| First Author | Xu S | Year | 2000 |
| Journal | Int Immunol | Volume | 12 |
| Issue | 3 | Pages | 397-404 |
| PubMed ID | 10700474 | Mgi Jnum | J:61130 |
| Mgi Id | MGI:1354477 | Doi | 10.1093/intimm/12.3.397 |
| Citation | Xu S, et al. (2000) B cell development and activation defects resulting in xid-like immunodeficiency in BLNK/SLP-65-deficient mice. Int Immunol 12(3):397-404 |
| abstractText | 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-gamma, 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. |
