Reduced notch activity is associated with an impaired marginal zone B cell development and function in Sly1

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• 作者：Tanja Scheikl ; Bernhard Reis ; Klaus Pfeffer ; Bernhard Holzmann ; S ; ra Beer
• 关键词：Notch ; Marginal zone B cells ; T-independent antibody response
• 刊名：Molecular Immunology
• 出版年：2009
• 出版时间：February 2009
• 年：2009
• 卷：46
• 期：5
• 页码：969-977
• 全文大小：927 K

文摘

MZ B cells represent a distinct lineage of naive B lymphocytes, apart from FO B cells and peritoneal B1 cells, and mediate humoral immune responses against blood-borne type 2 T-independent antigens. Regulation of MZ B cell development involves the Notch receptor signaling, the intensity of B cell receptor signals, and cell compartmentalization by adhesion and chemokine receptors. Our previous work showed that gene-targeted mice expressing a truncated form of the putative signaling adapter protein SLy1 exhibit reduced numbers of a splenic B cell population enriched in MZ B cells. Here, we demonstrate that Sly1^d/d mice exhibit a partial, but selective, block in the transition from pre-MZ to mature MZ B cells. Development of both T1 and T2 precursor subsets and FO B cells was normal in Sly1^d/d mice. Consistent with the loss of MZ B cells, the production of antigen-specific IgM antibodies following immunization with pneumococcal polysaccharides was severely impaired in Sly1^d/d mice. Importantly, expression of the Notch signaling mediator RBP-J and the Notch target genes Hes-1 and Hes-5 was markedly reduced in MZ but not FO B cells of Sly1^d/d mice. In contrast, B cell receptor signaling, expression and function of LFA-1 and α4-integrins, and expression of chemokine receptors appeared intact in Sly1^d/d cells. Collectively, these results provide strong evidence that SLy1 is important for the generation and function of MZ B cells and suggest a novel link between SLy1 and the activity of the Notch pathway in the development of MZ B cells.