B cell development and activation defects resulting in xid-like immunodeficiency in BLNK/SLP-65-deficient mice

Int Immunol. 2000 Mar;12(3):397-404. doi: 10.1093/intimm/12.3.397.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibodies, Anti-Idiotypic / immunology
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology*
  • Bone Marrow / pathology
  • CD5 Antigens / analysis
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Differentiation
  • Humans
  • Immunoglobulin D / analysis
  • Immunoglobulin M / analysis
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology
  • Lymph Nodes / pathology
  • Lymphocyte Activation*
  • Mice
  • Mice, Knockout
  • Peritoneal Cavity / pathology
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Signal Transduction
  • Spleen / pathology


  • Adaptor Proteins, Signal Transducing
  • Antibodies, Anti-Idiotypic
  • B cell linker protein
  • CD5 Antigens
  • Carrier Proteins
  • Immunoglobulin D
  • Immunoglobulin M
  • Phosphoproteins
  • anti-IgM