Differing Requirements for MALT1 Function in Peripheral B Cell Survival and Differentiation

Abstract

During a T cell-dependent immune response, formation of the germinal center (GC) is essential for the generation of high-affinity plasma cells and memory B cells. The canonical NF-κB pathway has been implicated in the initiation of GC reaction, and defects in this pathway have been linked to immune deficiencies. The paracaspase MALT1 plays an important role in regulating NF-κB activation upon triggering of antigen receptors. Although previous studies have reported that MALT1 deficiency abrogates the GC response, the relative contribution of B cells and T cells to the defective phenotype remains unclear. We utilized chimeric mouse models to demonstrate that MALT1 function is required in B cells for GC formation. This role is restricted to BCR signaling where MALT1 is critical for B cell proliferation and survival. Moreover, the pro-apoptotic signal transmitted in the absence of MALT1 is dominant to the pro-survival effects of T cell-derived stimuli. In addition to GC B cell differentiation, MALT1 is required for plasma cell differentiation, but not mitogenic responses. Lastly, we show that ectopic expression of Bcl-2 can partially rescue the GC phenotype in MALT1-deficient animals by prolonging the lifespan of BCR-activated B cells, but plasma cell differentiation and antibody production remain defective. Thus, our data uncover previously unappreciated aspects of MALT1 function in B cells and highlight its importance in humoral immunity.

A MALT1 inhibitor suppresses human myeloid DC, effector T-cell and B-cell responses and retains Th1/regulatory T-cell homeostasis

“…MALT1 inhibition thus affects this extracellular dectin-mediated sensing for pathogens through a non-canonical caspase-8-dependent inflammasome activation. The obvious risk related to MALT1 inhibition is thus susceptibility to infections, particularly to fungal infections due to the link between dectin, MALT1, IL-1β and IL-17 [ 37 ]. This risk may be further potentiated by the effects of MALT1 inhibition on Th17 cells.…”

“…This may indicate that the regulation of NF-κB activation by MALT1 is less important for B-cell receptor mediated signalling than T-cell receptor signalling. In chimeric mouse model, the role of MALT1 has been demonstrated to be crucial for B-cell proliferation and differentiation [37]. B-cells may also participate in the presentation of autoantigens and inhibition of the proliferation of B-cells may be beneficial in this mechanism.…”

Carbohydrate-dependent B cell activation by fucose-binding bacterial lectins

“…The total B cell numbers in the spleens of BambL-treated mice were markedly increased, mainly due to the changes in the numbers of MFo, T1, and T2/3 populations ( on January 20, 2020 http://stke.sciencemag.org/ Downloaded from the para-caspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1) have been described to play essential roles in B cell differentiation, death, and survival (59,66,67).…”

Combination effect of laser diode for photodynamic therapy with doxycycline on a wistar rat model of periodontitis

“…Porphyromonas gingivalis has been reported as a bacterium that causes damage to the bone tissue through LPS virulence factors that inhibit osteoblast differentiation [ 8 ]. Alveolar bone damage in the periodontal tissue is characterized by bone resorption in the bone tissue, known as resorption bays (lacuna howship) [ 30 ]. Osteoclasts, cells that cause bone resorption, are branched motile cells with many nuclei; they are usually located in the lacuna howship [ 31 ].…”

“…Histomorphometric observation results showed a significant increase in the CEJ-AV distance in the healthy group and the periodontitis group. This increase is believed to be the result of bone resorption indicator that occurs in the alveolar bone and become popular method used by many researchers [ 4 , 5 , 30 ].…”