SummaryIn rabbits nearly all B lymphocytes express the glycoprotein CD5, in contrast to mice and humans, where only a small proportion of B cells express this molecule (Raman, C., and K.L. Knight. 1992.J. Immunol. 149:3858-3864). CD5 + B cells appear to develop early in ontogeny and be maintained throughout life by self-renewal. The function of CD5 on B cells is still unknown. We showed earlier that "positive" selection occurs during B lymphocyte development in the rabbit appendix. This selection favors B cells expressing surface immunoglobulins with VHa2 structures in the first and third framework regions (Pospisil, P,.., G.O. Young-Cooper, and tL.G. Mage. 1995. Proc. Natl. Acad. Sci. USA. 92:6961-6965). Here we report that F(ab')2 fragments, especially those bearing VHa2 framework region determinants, specifically interact with the B cell-surface glycoprotein CD5. This interaction can be inhibited by anti-CD5 antibodies. Furthermore, immobilized F(ab')2 fragments selectively bind CD5 molecules in appendix cell lysates. Interactions of V H framework region structures with CD5 may affect maintenance and selective expansion of particular B cells and thus contribute to autostimulatory growth of autoimmune or transformed cells.

B cells with a rearranged heavy-chain variable region VHa allotype-encoding VHI gene segment predominate throughout the life of normal rabbits and appear to be the source of the majority of serum immunoglobulins, which thus bear VHa allotypes. The functional role(s) of these VH framework region (FR) allotypic structures has not been defined. We show here that B cells expressing surface immunoglobulin with VHa2 allotypic specificities are preferentially expanded and positively selected in the appendix of young rabbits. By flow cytometry, a higher proportion of a2+ B cells were progressing through the cell cycle (S/G2/M) compared to a2-B cells, most of which were in the G1/GO phase of the cell cycle. The majority of appendix B cells in dark zones of germinal centers of normal 6-week-old rabbits were proliferating and very little apoptosis were observed. In contrast, in 6-week-old VH-mutant ali/ali rabbits, little cell proliferation and extensive apoptosis were observed. Nonetheless even in the absence of VH1, B cells with a2-like surface immunoglobulin had developed and expanded in the appendix of 11-weekold mutants. The numbers and tissue localization of B cells undergoing apoptosis then appeared similar to those found in 6-week-old normal appendix. Thus, B cells with immunoglobulin receptors lacking the VHa2 allotypic structures were less likely to undergo clonal expansion and maturation. These data suggest that "positive" selection of B lymphocytes through FR1 and FR3 VHa allotypic structures occurs during their development in the appendix.

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