PREFERENTIAL EXPANSION AND SURVIVAL OF B-LYMPHOCYTES BASED ON V-H FRAMEWORK-1 AND FRAMEWORK-3 EXPRESSION - POSITIVE SELECTION IN APPENDIX OF NORMAL AND V-H-MUTANT RABBITS

B cells with a rearranged heavy-chain variable region V(H)a allotype-e ncoding V(H)1 gene segment predominate throughout the life of normal r abbits and appear to be the source of the majority of serum immunoglob ulins, which thus bear V(H)a allotypes, The functional role(s) of thes e V-H framework region (FR) allotypic structures has not been defined, We show here that B cells expressing surface immunoglobulin with V(H) a2 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/G(2)/M) compared to a2(-) B cells, most of which were in the G(1)/G( 0) phase of the cell cycle. The majority of appendix B cells in dark z ones of germinal centers of normal 6-week-old rabbits were proliferati ng and very little apoptosis were observed. In contrast, in 6-week-old V-H-mutant ali/ali rabbits, little cell proliferation and extensive a poptosis were observed, Nonetheless even in the absence of V(H)1, B ce lls with a2-like surface immunoglobulin had developed and expanded in the appendix of 11-week-old mutants, The numbers and tissue localizati on of B cells undergoing apoptosis then appeared similar to those foun d in 6-week-old normal appendix. Thus, B cells with immunoglobulin rec eptors lacking the V(H)a2 allotypic structures were less likely to und ergo clonal expansion and maturation, These data suggest that ''positi ve'' selection of B lymphocytes through FR1 and FR3 V(H)a allotypic st ructures occurs during their development in the appendix.