Repertoire selection by pre-B-cell receptors and B-cell receptors, and genetic control of B-cell development from immature to mature B cells

During B-cell development the surrogate light (SL) chain is selectively exp ressed in progenitor and precursor Bcells during the developmental stages o f D-H to J(H) and V-H to D(H)J(H) rearrangements. Approximately half of all mu H chains produced by these rearrangements cannot pair with SL chains an d cannot form a pre-B-cell receptor (pre-BCR). A spectrum of affinities bet ween VpreB and individual V-H, domains generates preB cells with pre-BCR of different fitness which, in turn, determines the extent of the pre-B II-ce ll proliferation and the fidelity of allelic exclusion of the H chain locus . Once pre-BCR is expressed, SL chain expression is turned off. As pre-B II cells proliferate, SL is diluted out. thus limiting pre-BCR formation. As a consequence, pre-B II cells stop proliferating, become small and resting and begin to rearrange the L chain loci. Multiple rearrangements of the kap pa L chain alleles are often detected in wild-type small pre-B II cells. Ar ound 20% of the mu H chain-expressing small pre-B II cells also express L c hains but do not display the Ig on the surface. Hence, it is likely that no t all L chains originally generated in resting pre-B II cells can pair with the mu H chain previously present in that cell. The best fitting ones are selected preferentially to generate slg(+) B cells. Futhermore. the transit ion of immature B cells from the bone marrow to spleen and their developmen t to mature cells appear as two separate steps controlled by different gene s.