Abstract
The generation of a potent humoral immune response by B cells relies on the integration of signals induced by the B cell receptor, toll-like receptors and both negative and positive co-receptors. Several reports also suggest that integrin signaling plays an important role in this process. How integrin signaling is regulated in B cells is however still partially understood. Integrin activity and function are controlled by several mechanisms including regulation by molecular adaptors of the paxillin family. In B cells, Leupaxin (Lpxn) is the most expressed member of the family and in vitro studies suggest that it could dampen BCR signaling. Here, we report that Lpxn expression is increased in germinal center B cells compared to naïve B cells. Moreover, Lpxn deficiency leads to decreased B cell differentiation into plasma cells in vitro. However, Lpxn seems dispensable for the generation of a potent B cell immune response in vivo. Altogether our results suggest that Lpxn is dispensable for T-dependent and T-independent B cell immune responses.
Highlights
B cells and plasma cells (PCs), corresponding to the terminal step of B cell differentiation, are key players of humoral immunity
In order to characterize whether Lpxn plays a role in B cell activation and subsequently on germinal centers (GC) B cell biology we obtained a Lpxn deficient mouse model created by the Sanger Institute Mouse Resource via a “knockout first” approach leading to the generation of a total knockout [31] (Supplementary Figure 2A)
Of note the gene dose effect observed for Lpxn expression in Lpxn+/+, Lpxn+/−, and Lpxn−/− mice does not translate into differential PC differentiation
Summary
B cells and plasma cells (PCs), corresponding to the terminal step of B cell differentiation, are key players of humoral immunity. B cells can either differentiate rapidly into PCs through the extrafollicular response or, following cooperation with T cells they can generate germinal centers (GC). In this structure B cells have an intense proliferative activity and are submitted to two genetic modification processes; somatic hypermutation (SHM) and class switch recombination (CSR) to improve respectively the affinity and effector properties of their B cell antigen receptor (BCR). Integrins control B cell migration and adhesion [10,11,12] but their role is not limited to slowing down B cells They control the threshold of antigen-mediated signaling required for the full activation of B cells notably via the VLA4/VCAM1 complex [13]
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