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The RNA-binding protein polypyrimidine tract-binding protein-1 (Ptbp1) binds to the pyrimidine-rich sequence of target RNA and controls gene expression via post-transcriptional regulation such as alternative splicing. Although Ptbp1 is highly expressed in B lymphocytes, its role to date is largely unknown. To clarify the role of Ptbp1 in B-cell development and function, we generated B-cell-specific Ptbp1-deficient (P1BKO) mice. B-cell development in the bone marrow, spleen and peritoneal cavity of the P1BKO mice was nearly normal. However, the P1BKO mice had significantly lower levels of natural antibodies in serum compared with those of the control mice. To investigate the effect of Ptbp1 deficiency on the immune response in vivo, we immunized the P1BKO mice with T-cell-independent type-2 (TI-2) antigen NP-Ficoll and T-cell-dependent (TD) antigen NP-CGG. We found that B-cell-specific Ptbp1 deficiency causes an immunodeficiency phenotype due to defective production of antibody against both TI-2 and TD antigen. This immunodeficiency was accompanied by impaired B-cell receptor (BCR)-mediated B-cell activation and plasmablast generation. These findings demonstrate that Ptbp1 is essential for the humoral immune response. [ABSTRACT FROM AUTHOR]

Cross-linking of the high-affinity IgE receptor (FcεRI) on mast cells by IgE–antigen complex triggers signal transduction cascades leading to the release of inflammatory mediators and production of cytokines, which are critical for the development of allergic reactions. We have identified a novel member of the BASH/SLP-76 immunoreceptor-coupled adaptor family expressed in mast cells, termed MIST (for mast cell immunoreceptor signal transducer), which has later been found to be identical to a recently reported cytokine-dependent hemopoietic cell linker, Clnk. Upon FcεRI cross-linking, MIST/Clnk is tyrosine phosphorylated and associates with signaling proteins, phospholipase Cγ, Vav, Grb2 and linker for activation of T cells (LAT). Overexpression of a mutant form of MIST/Clnk inhibited FcεRI-mediated degranulation, increase in intracellular Ca2+, NF-AT activation and phosphorylation of LAT. As a crucial signaling component for FcεRI-induced mast cell degranulation, MIST/Clnk might serve as a target for anti-allergic therapy. [ABSTRACT FROM PUBLISHER]