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Mouse Variable‐Region Gene Families: Complexity, Polymorphism and Use in non‐Autoimmune Responses

During B-cell ontogeny, functional immunoglobulin (Ig) genes are generated by somatic juxtaposition of gene segments separated in the germline and termed variable (V), diversity (D, heavy chain only) and joining (J) gene segments (reviewed in (Tonegawa 1983, Alt et al. 1986)). V genes encode all residues of the first and second complementarity-determining region (CDR) of both heavy (H) and light (L) chains as well as part of the L chain CDR-3, and hence contribute the majority of antigen contact residues (Kabat et al. 1991). In human and murine systems, a considerable number of highly polymorphic VH and VL gene segments exist in the germline and, for practical reasons, have been classified into V-gene families and V-region protein groups. The complexity of V-gene families, their chromosomal organization and degree of polymorphism, and their usage in various responses has been studied in great detail. In an attempt to better understand autoimmune diseases, the present volume addresses the expression of these V genes and V-gene families in response to self antigens. This chapter introduces Ig genetics in the mouse, summarizes current Vgene and V-region protein classifications, reviews the complexity, chromosomal organization and polymorphism of the V-gene repertoire, and discusses V-gene usage in different B-cell repertoires and in response to complex foreign antigens to allow comparisons with V-gene usage in autoantibodies described throughout this volume. Lambda L chains are not included since they make up only a few percent of total mouse serum Ig and are rarely found in autoantibodies. Furthermore, the large body of data on V-gene usage in hapten responses will