NDLI: The B cell-restricted adaptor BASH is required for normal development and antigen receptor-mediated activation of B cells

Content Provider	PubMed Central
Author	Hayashi, Katsuhiko Ryo, Nittono Okamoto, Noriaki Tsuji, Sachiyo Hara, Yasushi Ryo, Goitsuka Kitamura, Daisuke
Copyright Year	2000
Abstract	B cell antigen receptor signals development, activation, proliferation, or apoptosis of B cells depending on their condition, and its proper signaling is critical for activation and homeostasis of the immune system. The B cell-restricted adaptor protein BASH (also termed BLNK/SLP-65) is rapidly phosphorylated by the tyrosine kinase Syk after BCR ligation and binds to various signaling proteins. BASH structurally resembles SLP-76, which is essential for T cell development and T cell receptor signaling. To evaluate the role for BASH in B cell development and function in vivo, we disrupted BASH alleles in embryonic stem cells by means of homologous recombination and used these cells to complement lymphocyte-incompetent blastocysts from RAG2-deficient mice. In the resultant chimeric mice, T cell development was apparently normal, but B cell development was impaired, and a normally rare population of large preB cells expressing preB cell receptor dominated in the bone marrow in place of small preB cells, although they were mostly noncycling. In addition, the mature B cell populations in the periphery and the bone marrow profoundly decreased in size, as did B-1 cells in the peritoneal cavity, and serum Ig was severely reduced. The BASH-deficient B cells scarcely proliferated or up-regulated B7-2 in response to BCR ligation and poorly proliferated upon CD40 ligation or lipopolysaccharide stimulation. This phenotype indicates that BASH is critical for preB cell receptor signaling inducing proliferation of large preB cells and the following differentiation, for peripheral B cell maturation, and for BCR signaling inducing activation/proliferation of B cells.
Starting Page	2755
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-03-14
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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