Delayed cellular maturation and decreased immunoglobulin kappa light chain production in immature B lymphocytes lacking B cell linker protein.
B cell linker (BLNK) protein is a component of the B cell receptor (BCR) signaling pathway and BLNK(-/-) mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. To study the effect of BLNK mutation at later stages of B cell development, we introduce an innocuous transgenic BCR into BLNK(-/-) mice and show that two populations of immature B cells distinguishable by their IgM(low (lo)) and IgM(high (hi)) phenotypes are found in the bone marrow of these mice in contrast to a single population of IgM(hi) cells found in control BCR-transgenic BLNK(+/+) mice. The mutant IgM(lo) and IgM(hi) cells are at an earlier developmental stage compared with the control IgM(hi) cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture. Thus, in the absence of BLNK the differentiation of immature B cells is delayed. Furthermore, mutant IgM(lo) cells produce equivalent level of immunoglobulin (Ig) mu but less Ig kappa proteins than control and mutant IgM(hi) cells and this defect is attributed to a decrease in the amount of kappa transcripts being generated. Finally, splenic B cells in BCR-transgenic BLNK(-/-) mice are predominantly of the transitional B cell phenotype and are rapidly lost from the peripheral B cell pool. Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of kappa light chain expression and continued immature B cell differentiation.
Xu
Shengli
S
Institute of Molecular and Cell Biology, Singapore 117609, Singapore.
Lam
Kong-Peng
KP
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D007075:Immunoglobulin M / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D004247:DNA