V-REGION DIRECTED SELECTION IN DIFFERENTIATING B-LYMPHOCYTES

We here analyse the repertoire of V(H)7183 rearrangements isolated from different stages of B cell differentiation in adult mice. The nucleotide sequence analyses of V(H)7183-D-J(H) rearrangements derived from large pre-B cells (B220+, mu-), small pre-B cells (B220+, mu-) and mature B cells (B220+, mu+) isolated from adult bone marrow revealed a sequential accumulation, among functional rearrangements, of D segments of the FL16 family and a depletion of D segments using the second and the third reading frame (RF). One member (V(H)7183.1) of the V(H)7183 gene family was utilized in 60-80% of the rearrangements of all populations analysed. In neonates the majority of the rearrangements utilizing this gene was found to be functional. In contrast, >96% of the V(H)7183 rearrangements isolated from adult spleen were non-functional. These data provide evidence for cellular selection of V(H) regions acting at different points of the B cell differentiation pathway and at the transition of B cells from the bone marrow to the periphery.