title: Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor Signaling in B1 but Not B2 B Cells.
abstract: B1 and B2 B cells differ in their ability to respond to T-cell-independent (TI) antigens. Here we report that the Src-family kinase (SFK) regulator CD148 has a unique and critical role in the initiation of B1 but not B2 cell antigen receptor signaling. CD148 loss-of-function mice were found to have defective B1 B-cell-mediated antibody responses against the T-cell-independent antigens NP-ficoll and Pneumovax 23 and had impaired selection of the B1 B cell receptor (BCR) repertoire. These deficiencies were associated with a decreased ability of B1 B cells to induce BCR signaling downstream of the SFK Lyn. Notably, Lyn appeared to be selectively regulated by CD148 and loss of this SFK resulted in opposite signaling phenotypes in B1 and B2 B cells. These findings reveal that the function and regulation of Lyn during B1 cell BCR signaling is distinct from other B cell subsets.
authors.affiliation: Howard Hughes Medical Institute, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, Departments of Medicine and of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Skrzypczynska
authors.affiliation: Howard Hughes Medical Institute, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, Departments of Medicine and of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA.
authors.forename: Jing W
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Howard Hughes Medical Institute, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, Departments of Medicine and of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-0795, USA. Electronic address: art.weiss@ucsf.edu.
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D019061:src-Family Kinases / Q000276:immunology*
chemical_list: D011947:Receptors, Antigen, B-Cell; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
keywords: B1 B cell; BCR; CD148; DEP-1; Lyn; Pneumovax 23; Ptprj; T-cell-independent