Tumor Biology

, Volume 37, Issue 1, pp 829–835 | Cite as

Adaptive B cell responses in rituximab-treated diffuse large B cell lymphoma patients during complete remission

  • Zhanshan Cha
  • Chen Li
  • Yan Zang
  • Haihui Gu
  • Huijun Guo
  • Jinqi Li
  • Yuan Fang
  • Thomas F. Petersen
  • Jing Li
  • Richard O. Karas
  • Michele L. Hamilton
  • Baohua Qian
Original Article

Abstract

Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen. Treatment using rituximab in combination with chemotherapy has dramatically improved overall survival rate of diffuse large B cell lymphoma (DLBCL). Since rituximab can deplete both lymphoma B cells and normal B cells, how rituximab-treatment affects normal B cell function in DLBCL patients under remission is unclear. Here, we examined peripheral blood B cell composition and antigen-specific B cell responses in DLBCL patients in remission and observed reductions in the frequencies of total B cell as well as several major B cell subsets, including CD19+IgD+ naive B cells, CD19+IgDCD27+ memory B cells, and CD19loCD27hi plasmablasts. Moreover, tetanus toxin (TT)-specific B cell proliferation was reduced in DLBCL patients in remission. On the other hand, HA-specific IgG-secreting B cell responses could be stimulated by influenza vaccination in DLBCL patients in remission, demonstrating that the machinery for generating de novo adaptive B cell responses was functional in DLBCL patients in remission. Our results provided insights in normal B cell function in DLBCL patients in remission.

Keywords

B cell Rituximab BLDCL Remission 

Notes

Conflict of interest

None

References

  1. 1.
    Horner MJ, Ries LAG, Krapcho M, Eisner MP, Kosary CL, Hankey BF, et al. SEER Cancer Statistics Review, 1975–2006. [Internet]. Statistics (Ber). 2006. Available from: http://seer.cancer.gov/csr/1975_2002/Google Scholar
  2. 2.
    Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435–45.PubMedGoogle Scholar
  3. 3.
    Molina A. A decade of rituximab: improving survival outcomes in non-Hodgkin’s lymphoma. Annu Rev Med. 2008;59:237–50.CrossRefPubMedGoogle Scholar
  4. 4.
    Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105:1417–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Robak T, Dmoszynska A, Solal-Céligny P, Warzocha K, Loscertales J, Catalano J, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010;28:1756–65.CrossRefPubMedGoogle Scholar
  6. 6.
    Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003;22:7359–68.CrossRefPubMedGoogle Scholar
  7. 7.
    Demidem A, Lam T, Alas S, Hariharan K, Hanna N, Bonavida B. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm. 1997;12:177–86.CrossRefPubMedGoogle Scholar
  8. 8.
    Jung D, Giallourakis C, Mostoslavsky R, Alt FW. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006;24:541–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Schatz DG, Ji Y. Recombination centres and the orchestration of V(D)J recombination. Nat Rev Immunol. 2011;11:251–63.CrossRefPubMedGoogle Scholar
  10. 10.
    Hardy RR, Hayakawa K. B cell development pathways. Annu Rev Immunol. 2001;19:595–621.CrossRefPubMedGoogle Scholar
  11. 11.
    Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621–63.CrossRefPubMedGoogle Scholar
  12. 12.
    Allen CDC, Okada T, Cyster JG. Germinal-center organization and cellular dynamics. Immunity. 2007;27(2):190–202.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Shaffer AL, Young RM, Staudt LM. Pathogenesis of human B cell lymphomas. Annu Rev Immunol. 2012;30:565–610.CrossRefPubMedGoogle Scholar
  14. 14.
    Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, et al. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature. 2009;459:717–21.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nussenzweig A, Nussenzweig MC. Origin of chromosomal translocations in lymphoid cancer. Cell. 2010;141(1):27–38.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117:5019–32.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Moir S, Fauci AS. B cells in HIV infection and disease. Nat Rev Immunol. 2009;9:235–45.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Geffroy-Luseau A, Chiron D, Descamps G, Jégo G, Amiot M, Pellat-Deceunynck C. TLR9 ligand induces the generation of CD20+ plasmablasts and plasma cells from CD27+ memory B-cells. Front Immunol. 2011;2:83.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med. 2009;361:1945–52.CrossRefPubMedGoogle Scholar
  20. 20.
    Harwood NE, Batista FD. Early events in B cell activation. Annu Rev Immunol. 2010;28:185–210.CrossRefPubMedGoogle Scholar
  21. 21.
    Bour-jordan H, Bluestone JA. Commentaries B cell depletion : a novel therapy for autoimmune diabetes ? J Clin Invest. 2007;117:3642–5.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annu Rev Immunol. 2011;29:273–93.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Nadler LM, Ritz J, Hardy R, Pesando JM, Schlossman SF, Stashenko P. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest. 1981;67:134–40.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Robillard N, Avet-Loiseau H, Garand R, Moreau P, Pineau D, Rapp MJ, et al. CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma. Blood. 2003;102:1070–1.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zhanshan Cha
    • 1
  • Chen Li
    • 2
  • Yan Zang
    • 1
  • Haihui Gu
    • 1
  • Huijun Guo
    • 1
  • Jinqi Li
    • 1
  • Yuan Fang
    • 3
  • Thomas F. Petersen
    • 3
  • Jing Li
    • 4
  • Richard O. Karas
    • 5
  • Michele L. Hamilton
    • 6
  • Baohua Qian
    • 1
  1. 1.Department of TransfusionChanghai Hospital, Second Military Medical UniversityShanghaiChina
  2. 2.Department of Hepatobiliary SurgeryLinyi People’s HospitalLinyiChina
  3. 3.BGC Biotechnology Research CenterJinanChina
  4. 4.Department of HematologyShandong Affiliated HospitalShandongChina
  5. 5.School of MedicineWayne State UniversityDetroitUSA
  6. 6.Department of MedicineUniversity of MarylandBaltimoreUSA

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