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+IgDhiIgMhiCD21/35hiCD23hi) 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.
Highlights
It is widely established that two signals are needed for the optimal activation of T cells
CD86 costimulation enhances the activation of Toll like Receptor-2 (TLR-2) stimulated resting B cells (RB) cells
We first investigated the impact of CD86 and Toll-like receptors (TLRs)-2 costimulation (TLR2.CD86) on RB cells (Fig. 1A)
Summary
It is widely established that two signals are needed for the optimal activation of T cells. Signal-2 is APC driven and engages interaction of costimulatory molecules, mainly CD80 and CD86 with CD28 and CTLA-4 that are expressed on T cells [1,2,3]. The role of costimulatory molecules is well established in the context of T cell activation but not much is known in the case of B cells [4,5,6]. Much evidence has been generated indicating the role of costimulatory molecules in influencing the functions of APCs through bi-directional signaling [7,8,9,10,11]. Direct triggering of B cells through CD86 enhances proliferation, secretion of IgG1 and IgG2a and their survival by augmenting the expression of anti-apoptotic molecules [11]. Cross linking of CD86 on human B cells that are stimulated in vitro with CD40 and cytokines enhances secretion of
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