Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65.
During signal transduction through the B cell antigen receptor (BCR), several signaling elements are brought together by the adaptor protein SLP-65. We have investigated the role of SLP-65 in B cell maturation and function in mice deficient for SLP-65. While the mice are viable, B cell development is affected at several stages. SLP-65-deficient mice show increased proportions of pre-B cells in the bone marrow and immature B cells in peripheral lymphoid organs. B1 B cells are lacking. The mice show lower IgM and IgG3 serum titers and poor IgM but normal IgG immune responses. Mutant B cells show reduced Ca2+ mobilization and reduced proliferative responses to B cell mitogens. We conclude that while playing an important role, SLP-65 is not always required for signaling from the BCR.
Jumaa
H
H
Max Planck Institute for Immunobiology, Freiburg, Germany.
Wollscheid
B
B
Mitterer
M
M
Wienands
J
J
Reth
M
M
Nielsen
P J
PJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000917:Antibody Formation; D016175:B-Lymphocyte Subsets; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005434:Flow Cytometry; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008213:Lymphocyte Activation / Q000502:physiology*; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology; D010750:Phosphoproteins; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D008934:Mitogens; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases