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Mechanisms controlling production of membrane and secreted immunoglobulin during B cell development

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Abstract

The immunoglobulin gene which encodes both membrane-associated and secreted proteins through alternative RNA processing reactions has been a model system used for over 25 yr to better understand the regulatory mechanisms governing alternative RNA processing. This gene contains competing cleavage-polyadenylation and RNA splicing reactions and the relative use of the two pathways is differentially regulated between B cells and plasma cells. General cleavage-polyadenylation and RNA splicing reactions are both altered during B cell maturation to affect immunoglobulin expression. However, the specific factors involved in this regulation have yet to be identified clearly. As transcriptional regulators stimulate the developmental RNA processing switch, microarray analysis is a promising approach to identify candidate regulators of this complex RNA processing mechanism.

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References

  1. Lin Y, Wong K, Calame K: Repression of c-myc transcription by Blimp-1, and inducer of terminal B cell differentiation. Science 1997;276:596–599.

    Article  PubMed  CAS  Google Scholar 

  2. Schliephake DE, Schimpl A: Blimp-1 overcomes the block in IgM secretion in lipopolysaccharide/anti-μ F(ab′)2-costimulated B lymphycytes. Eur J Immunol 1996;26:268–271.

    Article  PubMed  CAS  Google Scholar 

  3. Turner CA Jr, Mack DH, Davis MM: Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell 1994;77:297–306.

    Article  PubMed  CAS  Google Scholar 

  4. Lin K-I, Angelin-Duclos C, Kuo TC, Calame K: Blimp-1-dependent repression of Pax-5 is required for differentialtion of B cells to immunogloblulin M-secreting plasma cells. Mol Cell Biol 2002;22:4771–4780

    Article  PubMed  CAS  Google Scholar 

  5. Sciammas R, Davis MM: Modular natura of Blimp-1 in the regulation of gene expression during B cell maturation. J Immunol 2004;172:5427–5440.

    PubMed  CAS  Google Scholar 

  6. Shaffer AL, Lin KI, Kuo TC, et al: Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 2002;17 (1):51–62.

    Article  PubMed  CAS  Google Scholar 

  7. Yu J, Angelin-Duclos C, Greenwood J, Liao J, Calame K: Transcriptional repression by Blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Mol Cell Biol 2000;20:2592–2603.

    Article  PubMed  CAS  Google Scholar 

  8. Calame KL: Plasma cells: finding new light at the end of B cell development. Nat Immunol 2001;2(12): 1103–1108.

    Article  PubMed  CAS  Google Scholar 

  9. Calame KL, Lin KI, Tunyaplin C: Regulatory mechanisms that determine the development and function of plasma cells. Annu Rev Immunol 2003;21:205–230.

    Article  PubMed  CAS  Google Scholar 

  10. Sciammas R, Davis MM: Blimp-1; Immunoglobulin secretion and the switch to plasma cells. Curr Top Microbiol Immunol 2005;290:201–224.

    Article  PubMed  CAS  Google Scholar 

  11. Shapiro-Shelef M, Calame K: Regulation of plasmacell development. Nat Rev Immunol 2005;5(3): 230–242.

    Article  PubMed  CAS  Google Scholar 

  12. Brewer JW, Hendershot LM: Building an antibody factory: a job for the unfolded protein response. Nat Immunol 2005;6(1):23–29.

    Article  PubMed  CAS  Google Scholar 

  13. Koshland ME: The immuoglobulin helper: the J chain; in: Honjo T, Alt FW, Rabbitts TH (eds): Immunoglobulin Genes. London, Academic Press, 1989, pp. 345–359.

    Google Scholar 

  14. Sidman C: B lymphocyte differentiation and the control of IgM mu chain expression. Cell 1981;23 (2):379–389.

    Article  PubMed  CAS  Google Scholar 

  15. Hombach J, Sablitzky F, Rajewsky K, Reth M: Transfected plasmacytoma cells do not transport the membrane form of IgM to the cell surface. J Exp Med 1988;167(2):652–657.

    Article  PubMed  CAS  Google Scholar 

  16. Hombach J, Tsubata T, Leclercq L, Stappert H, Reth M: Molecular components of the B-cell antigen receptor complex of the IgM class. Nature 1990;343(6260): 760–762.

    Article  PubMed  CAS  Google Scholar 

  17. Kelley DE, Perry RP: Transcriptional and post-transcriptional control of immunoglobulin mRNA production during B lymphocyte development. Nucleic Acids Res 1986;14:5431–5447.

    Article  PubMed  CAS  Google Scholar 

  18. Lamson G, Koshland ME: Changes in J chain and μ chain RNA expression as a function of B cell differentiation. J Exp Med 1984;160:877–892.

    Article  PubMed  CAS  Google Scholar 

  19. Perry RP, Kelley DE: Immunoglobulin messenger RNAs in murine cell lines that have characteristics of immature B lymphocytes. Cell 1979;18:1333–1339.

    Article  PubMed  CAS  Google Scholar 

  20. Yuan D, Tucker PW: Transcriptional regulation of μ-δ heavy chain locus in normal murine B lymphocytes. J Exp Med 1984;160:564–583.

    Article  PubMed  CAS  Google Scholar 

  21. Mason JO, Williams GT, Neuberger MS: The half-life of immunoglobulin mRNA increases during B-cell differentiation: a possible role for targeting to membrane-bound ribosomes. Genes Dev 1988;2:1003–1011.

    Article  PubMed  CAS  Google Scholar 

  22. Reed DJ, Hawley J, Dang T, Yuan D: Role of differential mRNA stability in the regulated expression of IgM and IgD. J Immunol 1994;152:5330–5336.

    PubMed  CAS  Google Scholar 

  23. Jack HM, Wabl M: Immunoglobulin mRNA stability varies during B lymphocyte differentiation. EMBO J 1988;7(4):1041–1046.

    PubMed  CAS  Google Scholar 

  24. Yuan D, Dang T: Regulation of μm vs μs mRNA expression in an inducible B cell line. Mol Immunol 1989;26:1059–1067.

    Article  PubMed  CAS  Google Scholar 

  25. Milcarek C, Suda-Hartman M, Croll SC: Changes in abundance of IgG 2a mRNA in the nucleus and cytoplasm of a murine B-lymphoma before and after fusion to a myeloma cell. Mol Immunol 1996;33:691–701.

    Article  PubMed  CAS  Google Scholar 

  26. Blattner FR, Tucker PW: The molecular biology of immunoglobulin D. Nature 1984;307:417–422.

    Article  PubMed  CAS  Google Scholar 

  27. Mather EL, Nelson KJ, Haimovich J, Perry RP: Mode of regulation of immunoglobulin μ and δ-chain expression varies during B-lymphocyte maturation. Cell 1984;35:329–338.

    Article  Google Scholar 

  28. Maizels N: Immunoglobulin gene diversification. Annu Rev Genet 2005;39:23–46.

    Article  PubMed  CAS  Google Scholar 

  29. Alt FW, Bothwell ALM, Knapp M, et al: Synthesis of secreted and membrane-bound immunoglobulin mu heavy chains is directed by mRNAs that differ at their 3′ ends. Cell 1980;20:293–301.

    Article  PubMed  CAS  Google Scholar 

  30. Early P, Rogers J, Davis M, et al: Two mRNAs can be produced from a single immunoglobulin μ gene by alternative RNA processing pathways. Cell 1980; 20:313–319.

    Article  PubMed  CAS  Google Scholar 

  31. Rogers J, Early P, Carter C, et al: Two mRNAs with different 3′ ends encode membrane-bound and secreted forms of immunoglobulin μ chain. Cell 1980;20: 303–312.

    Article  PubMed  CAS  Google Scholar 

  32. Sharp PA: Split genes and RNA splicing. Cell 1994;77: 805–815.

    Article  PubMed  CAS  Google Scholar 

  33. International HGSC: Initial sequencing and analysis of the human genome. Nature 2001;409:860–921.

    Article  Google Scholar 

  34. Graveley BR: Sorting out the complexity of SR protein functions. RNA 2000;6:1197–1211.

    Article  PubMed  CAS  Google Scholar 

  35. Smith CWJ, Valcarcel J: Alternative pre-mRNA splicing: the logic of combinatorial control. TIBS 2000;25:381–388.

    PubMed  CAS  Google Scholar 

  36. Garcia-Blanco MA, Baraniak AP, Lasda EL: Alternative splicing in disease and therapy. Nat Biotechnol 2004;22(5):535–546.

    Article  PubMed  CAS  Google Scholar 

  37. Edwald-Gilbert G, Veraldi KL, Milcarek C: Alternative poly (A) site selection in complex transcription units: means to an end? Nucleic Acids Res 1997;25:2547–2561.

    Article  Google Scholar 

  38. Peterson ML. RNA processing and expression of immunoglobulin genes; in: Snow EC (ed) Handbook of B and T Lymphocytes. San Diego, Academic Press, 1994, pp. 321–342.

    Google Scholar 

  39. Peterson ML: Balanced efficiencies of splicing and cleavage-polyadenylation are required for μs and μm mRNA regulation. Gene Expr 1992;2:319–327.

    PubMed  CAS  Google Scholar 

  40. Peterson ML, Bertolino S, Davis F: An RNA polymerase pause site is associated with the immunoglobulin μs poly(A) site. Mol Cell Biol 2002;22:5606–5615.

    Article  PubMed  CAS  Google Scholar 

  41. Peterson ML, Bingham GL, Cowan C: Multiple features contribute to the use of the immunoglobulin M secretion-specific poly(A) signal but are not required for developmental regulation. Mol Cell Biol 2006;26(18):6762–6771.

    Article  PubMed  CAS  Google Scholar 

  42. Peterson ML, Bryman MB, Peiter M, Cowan C: Exon size affects competition between splicing and cleavagepolyadenylation in the immunoglobulin μ gene. Mol Cell Biol 1994;14:77–86.

    PubMed  CAS  Google Scholar 

  43. Peterson ML, Perry RP: Regulated production of μm and μs mRNA requires linkage of the poly(A) addition sites and is dependent on the length of the μs-μm intron. Proc Natl Sci USA 1986;83:8883–8887.

    Article  CAS  Google Scholar 

  44. Peterson ML, Perry RP: The regulated production of μm and μm mRNA is dependent on the relative efficiencies of μs poly(A) site usage and the Cμ4-to-MI splice. Mol Cell Biol 1989;9:726–738.

    PubMed  CAS  Google Scholar 

  45. Peterson ML: Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: non-Ig genes can be alternatively processed in B cells and plasma cells. Mol Cell Biol 1994; 14:7891–7898.

    PubMed  CAS  Google Scholar 

  46. Seipelt RL, Spear BT, Snow EC, Peterson ML: A nonimmunoglobulin transgene and the endogenous immunoglobulin μ gene are coordinately regulated by alternative RNA processing during B-cell maturation. Mol Cell Biol 1998;18:1042–1048.

    PubMed  CAS  Google Scholar 

  47. Lassman CR, Milcarek C: Regulated expression of the mouse γ2bIgH chain gene is influenced by poly(A) site order and strength. J Immunol 1992;148:2578–2585.

    PubMed  CAS  Google Scholar 

  48. Flaspohler JA, Milcarek C: Myelomas and lymphomas expressing the Ig γ2a H chain gene have similar transcription termination regions. J Immunol 1990;144:2802–2810.

    PubMed  CAS  Google Scholar 

  49. Lassman CR, Matis S, Hall BL, Toppmeyer DL, Milcarek C: Plasma cell-regulated polyadenylation at the Igμ2b secretion-specific poly(A) site. J Immunol 1992;148:1251–1260.

    PubMed  CAS  Google Scholar 

  50. Flaspohler JA, Boczkowski D, Hall BL, Milcarek C: The 3′-untranslated region of membrane exon 2 from the gamma 2a immunoglobulin gene contributes to efficient transcription termination. J Biol Chem 1995;270 (20):11903–11911.

    Article  PubMed  CAS  Google Scholar 

  51. Seipelt RL, Peterson ML: Alternative RNA processing of IgA pre-mRNA responds like IgM to alterations in the efficiency of the competing splice and cleavage-polyadenylation reactions. Mol Immunol 1995;32: 277–285.

    Article  PubMed  CAS  Google Scholar 

  52. Lebman DA, Park MJ, Fatica R, Zhang Z: Regulation of usage of membrane and secreted 3′ termini of α mRNA differs from μ mRNA. J. Immunol 1992:148: 3282–3289.

    PubMed  CAS  Google Scholar 

  53. Coyle JH, Borinstein SC, Woodward EO, Lebman DA: Predominant usage of the proximal poly(A) site in alpha mRNAs is not intrinsic to the 3′ termini. Int Immunol 1998;10(5):669–678.

    Article  PubMed  CAS  Google Scholar 

  54. Coyle JH, Lebman DA: Correct immunoglobulin α mRNA processing depends on specific sequence in the Cα3-αM intron. J Immunol 2000;164:3659–3665.

    PubMed  CAS  Google Scholar 

  55. Burnside RD, Peterson ML: The IgA gene contains multiple RNA polymerase pause sites downstream of the secretory-specific poly(A) site, 2006, to be published.

  56. Proudfoot NJ: How RNA polymerase II terminates transcription in higher eukaryotes. TIBS 1989; 14:105–110.

    PubMed  CAS  Google Scholar 

  57. Galli G, Guise JW, McDevitt MA, Tucker PW, Nevins JR: Relative position and strengths of poly(A) sites as well as trancription termination are critical to membrane versus secreted μ-chain expression during B-cell development. Genes Dev 1987;1:471–481.

    Article  PubMed  CAS  Google Scholar 

  58. Weiss EA, Michael A, Yuan D: Role of transcriptional termination in the regulation of μ mRNA expression in B lymphocytes. J Immunol 1989;143:1046–1052.

    PubMed  CAS  Google Scholar 

  59. Tisch R, Kondo N, Hozumi N: Parameters that govern the regulation of immunoglobulin δ heavy-chain gene expression. Mol Cell Biol 1990;10:5340–5348.

    PubMed  CAS  Google Scholar 

  60. Colgan DF, Manley JL: Mechanism and regulation of mRNA polyadenylation. Genes Dev 1997;11:2755–2766.

    PubMed  CAS  Google Scholar 

  61. Zhao J, Hyman L, Moore C: Formation of mRNA 3′ ends in eukaryotes: mechanism, regulation, and inter-relationships with other steps in mRNA synthesis. Microbiol Mol Biol Rev 1999;63:405–445.

    PubMed  CAS  Google Scholar 

  62. Berget S: Exon recognition in vertebrate splicing. J Biol Chem 1995;270:2411–2414.

    PubMed  CAS  Google Scholar 

  63. Manley J, Tacke R: SR proteins and splicing control. Genes Dev 1996;10:1569–1579.

    Article  PubMed  CAS  Google Scholar 

  64. Krecic AM, Swanson MS: hnRNP complexes: composition, structure, and function. Curr Opin Cell Biol 1999;11:363–371.

    Article  PubMed  CAS  Google Scholar 

  65. Charlet BN, Logan P, Singh G, Cooper TA: Dynamic antagonism between ETR-3 and PTB regulates cell type-specific alternative splicing. Mol Cell 2002;9(3): 649–658.

    Article  Google Scholar 

  66. Mayeda A, Krainer AR: Regulation of alternative splicing by hnRNP A1 and splicing factor SF2. Cell 1992;68:365–375.

    Article  PubMed  CAS  Google Scholar 

  67. Matis SA, Martincic K, Milcarek C: B-lineage regulated polyadenylation occurs on weak poly(A) sites regardless of sequence composition at the cleavage and downstream regions. Nucleic Acids Res 1996;24: 4684–4692.

    Article  PubMed  CAS  Google Scholar 

  68. Peterson ML, Gimmi ER, Perry RP: The developmentally regulated shift from membrane to secreted μ mRNA production is accompanied by an increase in cleavage-polyadenylation efficiency but no measurable change in splicing efficiency. Mol Cell Biol 1991;11:2324–2327.

    PubMed  CAS  Google Scholar 

  69. Yan D-H, Weiss EA, Nevins JR: Identification of an activity in B-cell extracts that selectively impairs the formation of an immunoglobulin μs poly(A) site processing complex. Mol Cell Biol 1995;15(4): 1901–1906.

    PubMed  CAS  Google Scholar 

  70. Takagaki Y, Seipelt RL, Peterson, ML, Manley JL: The polyadenylation factor CstF-64 regulates alternative processing of IgM heavy chain pre-mRNA during B cell differentiation. Cell 1996;87:941–952.

    Article  PubMed  CAS  Google Scholar 

  71. Edwalds-Gilbert G, Milcarek C: Regulation of poly(A) site use during mouse B-cell development involves a change in the binding of a general polyadenylation factor in a B-cell stage-specific manner. Mol Cell Biol 1995;15(11):6420–6429.

    PubMed  CAS  Google Scholar 

  72. Takagaki Y, Manley JL: Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation. Mol Cell 1998;2:761–771.

    Article  PubMed  CAS  Google Scholar 

  73. Takami Y, Kikuchi H, Nakayama T: Chicken histone deacetylase-2 controls the amount of the IgM H-chain at the steps of both transcription of its gene and alternative processing of its pre-mRNA in the DT40 cell line. J Biol Chem 1999;274:23977–23990.

    Article  PubMed  CAS  Google Scholar 

  74. Martincic K, Campbell R, Edwalds-Gilbert G, Souan L, Lotze MT, Milcarek C: Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the G0 to S phase transition. Proc Natl Acad Sci USA 1998;95:11095–11100.

    Article  PubMed  CAS  Google Scholar 

  75. Veraldi KL, Arhin G, Martincic K, Chung-Ganster L-H, Wilusz J, Milcarek C: hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells. Mol Cell Biol 2001;21:1228–1238.

    Article  PubMed  CAS  Google Scholar 

  76. Bagga PS, Arhin GK, Wilusz J: DSEF-1 is a member of the hnRNP H family of RNA-binding proteins and stimulates pre-mRNA cleavage and polyadenylation in vitro. Nucleic Acids Res 1998;26(23):5343–5350.

    Article  PubMed  CAS  Google Scholar 

  77. Matunis MJ, Xing J, Dreyfuss G. The hnRNP F protein: unique primary structure nucleicacid-binding properties, and subcellular localization. Nucleic Acids Res 1994;22(6):1059–1067.

    Article  PubMed  CAS  Google Scholar 

  78. Caputi M, Zahler AM: Determination of the RNA binding specificity of the heterogeneous nuclear ribonucleoprotein (hnRNP) H/H'/F/2H9 family. J Biol Chem 2001;276:43850–43859.

    Article  PubMed  CAS  Google Scholar 

  79. Phillips C, Jung S, Gunderson SI: Regulation of nuclear poly(A) addition controls the expression of immunoglobulin M secretory mRNA. EMBO J 2001; 20(22):6443–6452.

    Article  PubMed  CAS  Google Scholar 

  80. Phillips C, Pachikara N, Gunderson SI: U1A inhibits cleavage at the immunoglobulin M heavy-chain secretory poly(A) site by binding between the two downstream GU-rich regions. Mol Cell Biol 2004;24(14): 6162–6171.

    Article  PubMed  CAS  Google Scholar 

  81. Ma J, Gunderson SI, Phillips C: Non-snRNP U1A levels decrease during mammalian B-cell differentiation and release the IgM secretory poly(A) site from repression. RNA 2006;12(1):122–132.

    Article  PubMed  CAS  Google Scholar 

  82. Milcarek C, Martinçic K, Chung-Ganster L-H, Lutz CS: The snRNP-associated U1A levels change following IL-6 stimulation of human B cells. Mol Immunol 2003;39:809–814.

    Article  PubMed  CAS  Google Scholar 

  83. Tsurushita N, Ho L, Korn LJ: Nuclear factors in B lymphoma enhance splicing of mouse membrane-bound μ mRNA in Xenopus oocytes. Science 1988;239:494–497.

    Article  PubMed  CAS  Google Scholar 

  84. Bruce SR, Dingle RWC, Peterson ML: B-cell and plasma-cell splicing differences: a potential role in regulated immunoglobulin RNA processing. RNA 2003; 9:1264–1273.

    Article  PubMed  CAS  Google Scholar 

  85. Niwa M, Berget SM: Mutation of the AAUAAA polyadenylation signal depresses in vitro splicing of proximal but not distal introns. Genes Dev 1991;5: 2086–2095.

    Article  PubMed  CAS  Google Scholar 

  86. Niwa M, Rose SD, Berger SM: In vitro polyadenylation is stimulated by the presence of an upstream intron. Genes Dev 1990;4:1552–1559.

    Article  PubMed  CAS  Google Scholar 

  87. Ashe MP, Griffin P, James W, Proudfoot NJ: Poly(A) site selection in the HIV-1 provirus: inhibition of promoter-proximal polyadenylation by the downstream major splice donor site. Genes Dev 1995;9:3008–3025.

    Article  PubMed  CAS  Google Scholar 

  88. Furth P, Choe W, Rex J, Byrne JC, Baker C: Sequences homologous to 5′ splice sites are required for the inhibitory activity of papillomavirus late 3′ untranslated regions. Mol Cell Biol 1994;14:5278–5289.

    PubMed  CAS  Google Scholar 

  89. Kornblihtt AR, de la Mata M, Fededa JP, Munoz MJ, Nogues G: Multiple links between transcription and splicing. RNA 2004;10(10):1489–1498.

    Article  PubMed  CAS  Google Scholar 

  90. Bentley D: Coupling RNA polymerase II transcription with pre-mRNA processing. Curr Opin Cell Biol 19:11:347–351.

  91. Hirose Y, Manley JL: RNA polymerase II and the integration of nuclear events. Genes Dev 2000;14: 1415–1429.

    PubMed  CAS  Google Scholar 

  92. Proudfoot NJ: Connecting transcription to messenger RNA processing. Trends Biochem Sci 2000;25:290–293.

    Article  PubMed  CAS  Google Scholar 

  93. Proudfoot NJ, Furger A, Dye MJ: Integrating mRNA processing with transcription. Cell 2002;108:501–512.

    Article  PubMed  CAS  Google Scholar 

  94. Roberts GC, Gooding C, Mak HY, Proudfoot NJ, Smith CWJ: Co-transcriptional commitment to alternative splice site selection. Nucleic Acids Res 1998;26:5568–5572.

    Article  PubMed  CAS  Google Scholar 

  95. de la Mata M, Alonso CR, Kadener S et al: A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell 2003;12(2):525–532.

    Article  PubMed  Google Scholar 

  96. Robson-Dixon ND, Garcia-Blanco MA: MAZ elements alter transcription elongation and silencing of the fibroblast growth factor receptor 2 exon IIIb. J Biol Chem 2004;279:29075–29084.

    Article  PubMed  CAS  Google Scholar 

  97. Chalfant CE, Watson JE, Bisnauth LD et al: Insulin regulates protein kinase CβII expression through enhanced exon inclusion in L6 skeletal muscle cells. J Biol Chem 1998;273:910–916.

    Article  PubMed  CAS  Google Scholar 

  98. van der Houven, van Oordt W, Diaz-Meco MT, Lozano J, Krainer AR, Moscat J, Caceres JF: The MK 3/6-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. J Cell Biol 2000;149:307–316.

    Article  Google Scholar 

  99. Alizadeh AA, Eisen MB, Davis RE, et al Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403(6769):503–511.

    Article  PubMed  CAS  Google Scholar 

  100. Alizadeh A, Eisen M, Davis RE, et al: The lymphochip: a specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant lymphocytes. Cold Spring Harb Symp Quant Biol 1999;64:71–78.

    Article  PubMed  CAS  Google Scholar 

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  1. Martha L. Peterson

    Present address: Department of Microbiology & Immunology, Molecular Genetics, University of Kentucky Medical Center, 800 Rose St., 108A Combs Building, 40536-0093, Lexington, NY

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  1. Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, 40536, Lexington, KY

    Martha L. Peterson

  2. the Lucille Parker Markey Cancer Center, University of Kentucky College of Medicine, 40536, Lexington, KY

    Martha L. Peterson

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Peterson, M.L. Mechanisms controlling production of membrane and secreted immunoglobulin during B cell development. Immunol Res 37, 33–46 (2007). https://doi.org/10.1007/BF02686094

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