The Journal of Experimental Medicine
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Published online 8 July 2002 doi:10.1084/jem.20020172
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© Rockefeller University Press, 0022-1007/2002/7/197/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 2, July 15, 2002 197-206

Delayed Cellular Maturation and Decreased Immunoglobulin {kappa} Light Chain Production In Immature B Lymphocytes Lacking B Cell Linker Protein

Shengli Xu and Kong-Peng Lam

Institute of Molecular and Cell Biology, Singapore 117609, Singapore

Address correspondence to Kong-Peng Lam, Institute of Molecular and Cell Biology, 30 Medical Dr., Singapore 117609, Singapore. Phone: 65-6874-3784; Fax: 65-6779-1117; E-mail: mcblamkp{at}imcb.nus.edu.sg

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 IgMlow (lo) and IgMhigh (hi) phenotypes are found in the bone marrow of these mice in contrast to a single population of IgMhi cells found in control BCR-transgenic BLNK+/+ mice. The mutant IgMlo and IgMhi cells are at an earlier developmental stage compared with the control IgMhi 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 IgMlo cells produce equivalent level of immunoglobulin (Ig) µ but less Ig {kappa} proteins than control and mutant IgMhi 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.

Key Words: B lymphocytes • B cell development • B cell receptor • signal transduction • adaptor protein


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