Abstract
Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40 - molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID), signifying class switch recombination (CSR). Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.
Highlights
Stimulation of B cells through antigen specific B cell receptor (BCR) leads to their activation, proliferation and differentiation to antibody secreting plasma cells
First we examined whether signaling through Toll like receptors (TLRs)-2 can render resting B (RB) cells responsive to CD40 costimulation
We found that TLR2.CD40 activated RB cells upregulated the expression of genes encoding TNF receptor super family member Tnfrsf13b, which plays an important role in B cell activation and differentiation
Summary
Stimulation of B cells through antigen specific B cell receptor (BCR) leads to their activation, proliferation and differentiation to antibody secreting plasma cells. Besides BCR, B cells express an array of molecules that assist in regulating both innate and adaptive immune responses. Such examples include costimulatory molecules involved in adaptive immunity and Toll like receptors (TLRs) responsible for innate immunity [1,2]. Synergism between BCR and TLRs augments expression of NF-kB, MAPK p38, leading to enhanced B cell activation, proliferation and differentiation [3,4,5]. We observed that cross-linking of CD40 significantly bolsters the activation, proliferation, differentiation, calcium flux, antigen uptake and ability to help CD4 T cells of TLR-2 stimulated RB cells
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