Rabbit Appendix: A Site of Development and Selection of the B Cell Repertoire

Abstract

The normal rabbit primarily rearranges a single (V_H1) gene to several D_H and J_H genes (Becker et al. 1990; Knight and Becker 1990; Allegrucci et al. 1991). Thus combinatorial diversity is limited in developing rabbit B lymphocytes. Cohn and Langman (1990) hypothesized that in the mouse, a “high copy number repertoire” encoded by combinations of germline genes provides prompt and early protection against common pathogens. In the chicken, with only one rearranging V_H and V_L, the high copy number repertoire, is generated in the bursa of Fabricius by gene conversion (Langman and Cohn 1993). In view of the smaller contribution of combinatorial diversity to the B cell repertoire in rabbit compared to mouse, perhaps the rabbit also uses a gene conversion-like mechanism to diversify its rearranged V_H1-D-J gene sequences and generate its primary repertoire (Becker and Knight 1990; reviewed in Knight 1992). Work in our laboratory has shown that the appendix is a site of such diversification of rearranged VDJ sequences in young rabbits. Rearranged V_H sequences from individual appendix follicles reveal clonal diversification by gene conversion-like and somatic hypermutation mechanisms (Weinstein et al. 1994a). In addition to diversification of V_H gene sequences by gene conversion, positive and negative selection events occur in this organ that may involve endogenous as well as exogenous “superantigen-like” signals (Pospisil at al. 1995, 1996a,b). These signals appear to lead to selective expansion of B cells bearing particular framework region sequences and apoptotic death of other.