creators_name: Jain, Shweta creators_name: Chodisetti, Sathi Babu creators_name: Agrewala, J N type: article datestamp: 2013-02-14 06:12:46 lastmod: 2013-02-14 06:12:46 metadata_visibility: show title: Combinatorial Signaling through TLR-2 and CD86 Augments Activation and Differentiation of Resting B Cells. ispublished: pub subjects: QR180 note: Open Access abstract: B cells are an integral component in mounting humoral immune responses and they are also crucial in programming T cell mediated immunity. Usually, B cell activation is initiated by recognition of antigen through B cell receptor (BCR), followed by its processing and presentation to T cells. But very little is known about BCR independent activation of B cells. Now, there is an increasing body of evidence indicating the combinatorial effect of innate and adaptive immune components in modulating the functions of B cells. In this study, we demonstrate the activation of resting B cells (RB) by simultaneous involvement of Toll like Receptor-2 (TLR-2) and costimulatory molecule, CD86. Interestingly, these B cells exhibited significant level of activation and proliferation. Furthermore, this process of activation leads to the differentiation of RB cells, preferably into marginal zone precursors (CD19(+)IgD(hi)IgM(hi)CD21/35(hi)CD23(hi)) in a shorter time window and showed increased secretion of IgG isotype. These RB cells also showed enhanced antigen uptake capacity. These observations were also substantiated by microarray gene expression results, which strengthen the notion that combinatorial signaling through innate and adaptive immune components enhances B cell mediated immune response. Thus, the present study elucidates a novel BCR independent B cell activation mechanism that links TLR-2 and CD86. Hence signaling of TLRs in conjunction with costimulatory molecules will substantially help in bolstering humoral immune response, which can be extrapolated to formulate vaccination strategies for diseases involving B cell-mediated immunity. date: 2013 date_type: published publication: PloS one volume: 8 number: 1 publisher: Public Library of Science pagerange: e54392 refereed: TRUE issn: 1932-6203 official_url: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054392 related_url_type: pub citation: Jain, Shweta and Chodisetti, Sathi Babu and Agrewala, J N (2013) Combinatorial Signaling through TLR-2 and CD86 Augments Activation and Differentiation of Resting B Cells. PloS one, 8 (1). e54392. ISSN 1932-6203 document_url: http://crdd.osdd.net/open/1289/1/agrewala2013.pdf