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B Cell Development and T-Dependent Antibody Response Are Regulated by p38γ and p38δ. | LitMetric

B Cell Development and T-Dependent Antibody Response Are Regulated by p38γ and p38δ.

Front Cell Dev Biol

Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.

Published: March 2020

AI Article Synopsis

  • p38 MAPK isoforms p38γ and p38δ are crucial for B cell differentiation and immune responses, especially in the spleen.
  • Mice lacking these isoforms showed no change in bone marrow B cell differentiation but had fewer peripheral B cells and altered differentiation patterns.
  • The absence of p38γ and p38δ reduced B cell activation and proliferation in response to certain signals and led to weaker antibody responses to T-dependent antigens.

Article Abstract

p38MAP kinase (MAPK) signal transduction pathways are important regulators of inflammation and the immune response; their involvement in immune cell development and function is still largely unknown. Here we analysed the role of the p38 MAPK isoforms p38γ and p38δ in B cell differentiation in bone marrow (BM) and spleen, using mice lacking p38γ and p38δ, or conditional knockout mice that lack both p38γ and p38δ specifically in the B cell compartment. We found that the B cell differentiation programme in the BM was not affected in p38γ/δ-deficient mice. Moreover, these mice had reduced numbers of peripheral B cells as well as altered marginal zone B cell differentiation in the spleen. Expression of co-stimulatory proteins and activation markers in p38γ/δ-deficient B cells are diminished in response to B cell receptor (BCR) and CD40 stimulation; p38γ and p38δ were necessary for B cell proliferation induced by BCR and CD40 but not by TLR4 signaling. Furthermore, p38γ/δ-null mice produced significantly lower antibody responses to T-dependent antigens. Our results identify unreported functions for p38γ and p38δ in B cells and in the T-dependent humoral response; and show that the combined activity of these kinases is needed for peripheral B cell differentiation and function.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105866PMC
http://dx.doi.org/10.3389/fcell.2020.00189DOI Listing

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