SRC-like adaptor protein regulates B cell development and function.
The avidity of BCRs and TCRs influences signal strength during processes of lymphocyte development. Avidity is determined by both the intrinsic affinity for Ag and surface levels of the Ag receptor. The Src-like adaptor protein (SLAP) is a regulator of TCR levels on thymocytes, and its deficiency alters thymocyte development. We hypothesized that SLAP, which is expressed in B cells, also is important in regulating BCR levels, signal strength, and B cell development. To test this hypothesis, we analyzed the B cell compartment in SLAP-deficient mice. We found increased splenic B cell numbers and decreased surface IgM levels on mature, splenic B cells deficient in SLAP. Immature bone marrow and splenic B cells from BCR-transgenic, SLAP-deficient mice were found to express higher surface levels of IgM. In contrast, mature splenic B cells from BCR-transgenic mice expressed decreased levels of surface BCR associated with decreased calcium flux and activation-induced markers, compared with controls. These data suggest that SLAP regulates BCR levels and signal strength during lymphocyte development.
Dragone
Leonard L
LL
Division of Pediatric Immunology/Rheumatology, Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
Myers
Margaret D
MD
White
Carmen
C
Sosinowski
Tomasz
T
Weiss
Arthur
A
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000172:deficiency / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology
D011947:Receptors, Antigen, B-Cell; C095148:Sla protein, mouse; D016392:Proto-Oncogene Proteins pp60(c-src)