title: RasGRP1 Is an Essential Signaling Molecule for Development of B1a Cells with Autoantigen Receptors.
abstract: B1a cells, particularly the PD-L2(+) B1a cell subset, are enriched with autoantigen-specific receptors. However, the underlying molecular mechanism responsible for the skewed selection of autoreactive B1a cells remains unclear. In this study, we find that B1 cells express only Ras guanyl nucleotide-releasing protein (RasGRP) 1, whereas B2 cells express mostly RasGRP3 and little RasGRP1. RasGRP1 is indispensable for transduction of weak signals. RasGRP1 deficiency markedly impairs B1a cell development and reduces serum natural IgM production; in particular, B1a cells that express autoantigen receptors, such as anti-phosphatidylcholine B1a cells, are virtually eliminated. Thus, unlike Btk and other signalosome components, RasGRP1 deficiency selectively affects only the B1a cell population with autoantigen receptors rather than the entire pool of B1a cells.
authors: Center for Oncology and Cell Biology, Feinstein Institute for Medical Research, Manhasset, NY 11030; bguo@nshs.edu.
authors: Benchang
authors: http://orcid.org/0000-0002-8590-0635
authors: B
authors: Guo
authors: Center for Oncology and Cell Biology, Feinstein Institute for Medical Research, Manhasset, NY 11030; Department of Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Manhasset, NY 11030; and Department of Molecular Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Manhasset, NY 11030.
authors: Thomas L
authors: TL
authors: Rothstein
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology*; D015151:Immunoblotting; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001324:Autoantigens; D020662:Guanine Nucleotide Exchange Factors; C112278:Rasgrp1 protein, mouse; D011947:Receptors, Antigen, B-Cell