Abstract
The variable regions of immunoglobulin heavy chains are encoded by the three germline gene segments: V(ariable), D(iversity) and J(oining). These segments are joined during precursor B cell differentiation to form a functional VHDJH variable region gene. In the mouse there are hundreds of different VH gene segments that can be subdivided into families based on nucleotide sequence homology (reviewed in Alt, et al., 1987). Various studies of transformed and normal murine B lineage cells have shown that chromosomal position of VH segments is a major determinant of their rearrangement frequency, resulting in a preferential rearrangement of VH segments proximal to the cluster of JH elements (Yancopoulos, et al., 1984, 1988; Reth, et al., 1986; Perlmutter, et al., 1985). This preferential rearrangement phenomenon leads to the biased expression of JH-proximal VH segments in primary B cell repertoires; for example, these gene segments are the major contributors to the Ig heavy chain mRNA produced by B lineage cells of the fetal liver (Yancopoulos, et al., 1988). In contrast, B cells in peripheral lymphoid organs of adult mice appear to utilize most VH segments at equal frequency; that is the representation of different families in the peripheral Ig heavy chain mRNA repertoire correlates with the complexity of each family and is not related to chromosomal position (Yancopoulos, et al., 1988; Dildrop, et al., 1985). These findings led to the proposal that an initially biased repertoire is randomized, probably by cellular mechanisms, in the transition from primary to peripheral lymphoid tissues (Yancopoulos, et al., 1988).
Keywords
- Gene Segment
- Howard Hughes Medical Institute
- Variable Region Gene
- Murine System
- Peripheral Lymphoid Tissue
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References
Alt FW, Blackwell TK, Yancopoulos GD (1987) Development of the primary antibody repertoire. Science 238: 1079–1087
Berman JE, Mellis SJ, Pollock R, Smith CL, Suh H, Heinke B, Kowal C, Surti U, Chess L, Cantor CR, Alt FW (1987) Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus. EMBO J. 7: 727–738
Dildrop R, Krawinkel U, Winter E, Rajewsky K (1985) VH-gene expression in murine lipopolysaccharide blasts distributes over the nine known VH-gene subgroups and may be random. Eur. J. Immunol. 15: 1154–1156
Holmberg D (1987) High connectivity, natural antibodies preferentially use 7183 and QUPC 52 VH families. Eur. J. Immunol. 17: 399
Kodaira M, Kinashi T, Umemura I, Matsuda F, Noma T, Ono Y, Honjo T (1986) Organization and evolution of variable region genes of the human immunoglobulin heavy chain. J. Mol. Biol. 190: 529–541
Malynn BA, Yancopoulos GD, Barth JE, Bosma CG, Bosma MJ, Bona C, Alt FW Developmental expression of murine VH gene families, submitted Perlmutter RM, Kearney JF, Chang SP, Hood LE (1985) Developmentally controlled expression of immunoglobulin VH genes. Science 227: 1597–1601
Rajewsky K, Forster I, Cumano A (1987) Evolutionary and somatic selection of the antibody repertoire in the mouse. Science 238: 1088
Reth MG, Jackson S „Alt FW (1986) VHDJH formation and DJH replacement during pre-B differentiation: non-random usage of gene segments. EMBO J. 5: 2131
Schroeder Jr, HW, Hillson JL, Perlmutter RM (1987) Early restriction of the human antibody repertoire. Science 238: 791–793
Yancopoulos GD, Desiderio SV, Paskind M, Kearney JF, Baltimore D, Alt FW (1984) Preferential utilization of the most JH proximal VH gene segments in pre-B cell lines. Nature 311: 727–733
Yancopoulos GD, Malynn BA, Alt FW (1988) Developmentally regulated and strain-specific expression of murine VH gene families. J. Exp. Med. 168: 417–435
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© 1990 Springer-Verlag Berlin Heidelberg
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Logtenberg, T., Berman, J.E., Alt, F.W. (1990). Organization and Expression of Human VH Genes. In: Demaine, A.G., Banga, JP., McGregor, A.M. (eds) The Molecular Biology of Autoimmune Disease. NATO ASI Series, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75133-2_1
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DOI: https://doi.org/10.1007/978-3-642-75133-2_1
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