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 expressed in progenitor and precursor Bcells during the developmental stages of 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 and cannot form a pre-B-cell receptor (pre-BCR). A spectrum of affinities between 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-cell 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 kappa L chain alleles are often detected in wild-type small pre-B II cells. Around 20% of the mu H chain-expressing small pre-B II cells also express L chains but do not display the Ig on the surface. Hence, it is likely that not 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 transition of immature B cells from the bone marrow to spleen and their development to mature cells appear as two separate steps controlled by different genes.