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In this study, we find that B1 cells express only Ras guanyl nucleotide\u2013releasing 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1502132","type":"journal-article","created":{"date-parts":[[2016,2,6]],"date-time":"2016-02-06T03:14:29Z","timestamp":1454728469000},"page":"2583-2590","source":"Crossref","is-referenced-by-count":20,"title":["RasGRP1 Is an Essential Signaling Molecule for Development of B1a Cells with Autoantigen Receptors"],"prefix":"10.1093","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8590-0635","authenticated-orcid":false,"given":"Benchang","family":"Guo","sequence":"first","affiliation":[{"name":"Center for Oncology and Cell Biology, Feinstein Institute for Medical Research , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L","family":"Rothstein","sequence":"additional","affiliation":[{"name":"Center for Oncology and Cell Biology, Feinstein Institute for Medical Research , Manhasset, NY 11030"},{"name":"Department of Medicine, Hofstra North Shore\u2013Long Island Jewish School of Medicine , Manhasset, NY 11030"},{"name":"Department of Molecular Medicine, Hofstra North Shore\u2013Long Island Jewish School of Medicine , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"2025030702143078500_r1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/ni1301","article-title":"Identification of a B-1 B cell-specified progenitor","volume":"7","author":"Montecino-Rodriguez","year":"2006","journal-title":"Nat. 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