Activation and signaling cascade of B lymphocytes

Abstract

On the cell membrane, B cells express immunoglobulins that are associated with a heterodimer that participates in the signalling cascade for the activation and the posterior differentiation in plasma cells that produce secreted antibodies. The great diversity of antibodies that exist in the organism, the sites of antigen recognition with different specificity and affinity, the co-expression of different isotypes of immunoglobulins(IgM and IgD) on the plasma membrane, and the differentiation between membrane and secreted immunoglobulins (mIgM and sIgM) can be explained by genetic rearrangements of the DNA and alternative splicing of the RNA. Phosphorylation reactions of the proteins result of fundamental importance for this process . In the activation , phosphatidylinositols participate in the production of phosphate-3 inositol (IP3), which increases the intracellular calcium levels, and of diacylglicerol (DAG), which activates proteinkinase C. On the other hand, BLNK protein, Tec kinases, PLC and GEF, Ras and Rac are activated and the MAP kinase pathway is stimulated. All these processes induce the activation of several transcription factors such as NF-κB, NFAT and AP-1, which regulate the transcription of several genes. Genetic immunodeficiencies
caused by mutations of the molecules involved in the signaling cascade of B cell receptor (BCR) activation produce different phenotypes, including the blockage of the transition from pro-B to pre-B cells. The use of gene therapies is of fundamental value for the proper functioning of the immune system. MicroRNAs(miRNAs) are endogenous molecules that have a fundamental role in the regulation of the expression of cellular mRNAs.