Silencing of B Cell Receptor Signals in Human Naive B Cells (original) (raw)
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Journal of Experimental Medicine, 2007
ginal zone B cell formation, was not due to diminished CD22 phosphorylation or inhibitory function. Microarray profi ling showed no evidence for enhanced signaling by the IgG tail for calcium/calcineurin, ERK, or nuclear factor κB response genes and little evidence for any enhanced gene induction. Instead, almost half of the antigen-induced gene response in IgM B cells was diminished 50-90% by the IgG tail segment. These fi ndings suggest a novel "less-is-more" hypothesis to explain how switching to IgG enhances B cell memory responses, whereby decreased BCR signaling to genes that oppose marginal zone and plasma cell differentiation enhances the formation of these key cell types. CORRESPONDENCE Christopher C. Goodnow: Chris.Goodnow@anu.edu.au Abbreviations used: BCR, B cell antigen receptor; ERK, extracellular signal-related kinase; HEL, hen egg lysozyme; ITAM, immunoreceptor tyrosine-based activation motif; MAP, mitogen-activated protein; MEK, MAP kinase/ ERK kinase; SHP-1, Src homology domain 2-containing protein tyrosine phosphatase.
Formation Differentiation and Memory Antigen-Dependent Murine B Cell
2000
Supplementary html http://www.jimmunol.org/content/suppl/2008/03/10/179.10.6808.DC1\. References http://www.jimmunol.org/content/179/10/6808.full#ref-list-1 , 42 of which you can access for free at: cites 92 articles This article Subscriptions http://jimmunol.org/subscriptions is online at: The Journal of Immunology Information about subscribing to
bca: an activation-related B-cell gene
Molecular Immunology, 1998
We have identified a novel activation related B-cell gene (her) through differential hybridization screening of a murine B cell cDNA library. The deduced amino acid sequence predicted a protein of 482 amino acids with strong sequence similarity to the SH2 and SH3 domains present within the non-catalytic regions of several protein tyrosine kinases. Northern analysis of RNA from several murine B-cell lines revealed a transcript of 1.8 kb. which was not detected in T-cell and non-lymphoid cell lines. hcu was transcribed at low levels in resting spleen cells from a variety of normal mouse strains and was strongly expressed in kidney RNA. hca expression was markedly increased in RNA prepared from mitogen activated B cells, and in freshly isolated spleen and lymph node cells of MRL:'lpr and NZB autoimmune strains. The unique sequence of ~CLI. which bears no obvious similarity to any specific class of proteins containing SH2 and SH3 domains, suggests that this gene encodes a novel protein potentially involved in B-cell signal transduction. 1~:'
The Journal of Immunology, 2008
Memory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their naive precursors is poorly understood. To address this, it would be important to understand how gene expression differs between memory and naive B cells to elucidate memory-specific functions. Using model systems that help overcome the lack of murine memory-specific markers and the low frequency of Ag-specific memory and naive cells, we undertook a global comparison of gene expression between memory B cells and their naive precursors. We identified genes with differential expression and confirmed the differential expression of many of these by quantitative RT-PCR and of some of these at the protein level. Our initial analysis revealed differential expression patterns of genes that regulate signaling. Memory B cells have increased expression of genes important in regulating adenosine signaling and...
B cell memory: how to start and when to end
Nature Immunology, 2009
B cell memory is a carefully orchestrated developmental program that requires antigen-specific CD4 + T cell help after the initial priming of naive B cells. Entry into germinal centers (GCs) signifies the beginning of diversification and selection that ends with the production of long-lived memory B cell compartments 1 . In this issue of Nature Immunology, studies led by Cornall and Goodnow 2 identify loss-of-function mutations in the gene encoding DOCK8, a member of the Rho-Rac family of GTP-exchange factors, that grossly disrupt affinity maturation and memory B cell development in the GC reaction. A second study by Weill and colleagues 3 documents extraordinary longevity for GCs initiated with particulate antigens. Both groups not only provide new insights into the regulation of antigen-specific B cell memory but also introduce valuable new animal models that will help guide future studies in this important research arena.
Regulation of the B Cell Receptor Repertoire
The TNF-family cytokine BAFF (BLyS) promotes B lymphocyte survival and is overexpressed in individuals with systemic lupus erythematosus and Sjögren's Syndrome. BAFF can rescue anergic autoreactive B cells from death, but only when competition from nonautoreactive B cells is lacking. Yet, high BAFF levels promote autoantibody formation in individuals possessing diverse B cells. To better understand how excess BAFF promotes autoimmunity in a polyclonal immune system, Ig L chain usage was analyzed in 3H9 site-directed IgH chain transgenic mice, whose B cells recognize DNA and chromatin when they express certain endogenous L chains. BAFF levels were manipulated in 3H9 mice by introducing transgenes expressing either BAFF or its natural inhibitor DBAFF. B cells in BAFF/3H9 mice were elevated in number, used a broad L chain repertoire, including L chains generating high-affinity autoreactivity, and produced abundant autoantibodies. Comparison of spleen and lymph node B cells suggested that highly autoreactive B cells were expanded. By contrast, DBAFF/3H9 mice had reduced B cell numbers with a repertoire similar to that of 3H9 mice, but lacking usage of a subset of Vk genes. The results show that limiting BAFF signaling only slightly selects against higher affinity autoreactive B cells, whereas its overexpression leads to broad tolerance escape and positive selection of autoreactive cells. The results have positive implications for the clinical use of BAFF-depleting therapy.