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Repertoire selection by pre‐B‐cell receptors and B‐cell receptors, and genetic control of B‐cell development from immature to mature B cells
Author(s) -
Melchers Fritz,
Ten Boekel Edwin,
Seidl Thomas,
Kong Xian Chu,
Yamagami Tamotsu,
Onishi Kazuo,
Shimizu Takeyuki,
Rolink Antonius G.,
Andersson Jan
Publication year - 2000
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2000.imr017510.x
Subject(s) - allelic exclusion , biology , b cell , immunoglobulin light chain , microbiology and biotechnology , b cell receptor , breakpoint cluster region , receptor , cell growth , antibody , genetics , t cell , t cell receptor , immune system
Summary: During B‐cell development the surrogate light (SL) chain is selectively expressed in progenitor and precursor B cells during the developmental stages of DH to JH and VH to DH JH rearrangements. Approximately half of all 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 VH 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 k L chain alleles are often detected in wild‐type small pre‐B II cells. Around 20% of the 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 H chain previously present in that cell. The best fitting ones are selected preferentially to generate sIg+ B cells. Furthermore, 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.