International Immunology, Vol. 12, No. 3, 397-404,
March 2000
© 2000 Japanese Society for Immunology
B cell development and activation defects resulting in xid-like immunodeficiency in BLNK/SLP-65-deficient mice
Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Drive, Singapore 117609, Republic of Singapore
Correspondence to: K.-P. Lam
Engagement of the B cell receptor (BCR) leads to the activation of tyrosine kinases and other signaling molecules that ultimately determine the type and magnitude of the B lymphocyte's cellular response. The adaptor protein BLNK/SLP-65 plays a pivotal role in BCR signal transduction by coupling Syk activation to downstream elements such as Grb2, phospholipase C-
, Vav and Nck. We have generated BLNK–/– mice to determine the physiological role of this protein in B cell development and activation. BLNK–/– mice exhibit an incomplete block in B cell development with a severe inhibition of pro-B to pre-B cell differentiation. BLNK–/– sIgM+ cells can develop, seed the peripheral lymphoid tissues and accumulate in numbers overtime. However, these mutant B cells failed to mature and are non-responsive to BCR cross-linking in terms of proliferation and up-regulation of activation markers such as CD69 and CD86 (B7-2). In addition, the CD5+ subset of B cells is absent. The immune response to T cell-independent antigen but not T cell-dependent antigen is also impaired. Overall, the phenotype of BLNK–/– mice bears a striking resemblance to that of xid mice which is the murine model of human XLA that has a mutation in Bruton's tyrosine kinase. This raises the interesting possibility that mutation in BLNK/SLP-65 may be responsible for certain human immunodeficiencies.
Keywords: adaptor protein, B cell antigen receptor, CD5+ B cells, signal transduction, gene targeting
Transmitting editor: D. Tarlinton
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