Understanding early morphological changes in B cell activation.

Abstract

B cells play a crucial role in the adaptive immune response by binding to an array of antigens and generating explicit responses against them. B cells sense the antigens through the surface expressed B cell receptors (BCRs). Antigen binding to the BCR initiates clustering of the BCRs that triggers a signaling cascade leading to the activation of MAP kinases and transcription of a variety of genes associated with B cell activation. In addition, antigen binding to the BCR also triggers the endocytosis of the antigen bound BCR and it’s trafficking to specialized intracellular compartments in which antigen processing occurs. Recently it has become clear that B cells, in addition to clonally expressed BCRs also express various germ line encoded pattern recognition receptors, in particular Toll like receptors (TLRs). TLRs are innate immune receptors that recognize conserved molecular patterns present in microbes, referred to as pathogen associated molecular patterns (PAMPs). This dual expression allows B cells to not only sense antigen but also survey their environment for danger signals associated with the presence of pathogens. Although both BCR and TLRs initiate signal independently, in response to antigens and PAMPs, B cells are able to integrate both antigen-specific and danger signals into a qualitatively and quantitatively unique molecular response. Indeed, TLRs have been shown to significantly influence the outcome of antigen engagement by the BCR and contribute to the immune dysregulation observed in autoimmune disease and in some B cell tumors. I have tried to study the early changes involved in B cell with response to TLR9 ligand. We have observed that some of these early events are manifested as morphological changes in B cells. Using field emission scanning electron microscopy and confocal microscopy, I have attempted to elucidate these preliminary changes. I have also planned an approach to look for the pathways involved in these morphological changes. Alongside, I have tried to check for some of the important molecules involved in the TLR9 ligand internalization and signaling.