Aberrant zonal recycling of germinal center B cells impairs appropriate selection in lupus.

Autor:	Sanchez GM; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Hirsch ES; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., VanValkenburg A; Division of Infectious Diseases, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Mayer DP; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Gbedande K; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Francis RL; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Song W; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA., Antao OQ; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Brimmer KE; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Lemenze A; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Stephens R; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Johnson WE; Division of Infectious Diseases, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, USA., Weinstein JS; Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Newark, NJ 07103, USA. Electronic address: jason.weinstein@rutgers.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Nov 26; Vol. 43 (11), pp. 114978. Date of Electronic Publication: 2024 Nov 10.
DOI:	10.1016/j.celrep.2024.114978
Abstrakt:	Autoimmune diseases such as lupus are characterized by polyclonal B cell activation, leading to the production of autoantibodies. The mechanism leading to B cell dysregulation is unclear; however, the defect may lie in selection within germinal centers (GCs). GC B cells cycle between proliferation and mutation in the dark zone and selection in the light zone (LZ). Temporal assessment of GCs from mice with either persistent infection or lupus showed an accumulation of LZ B cells. Yet, only in lupus, GC B cells exhibited reduced proliferation and progressive loss of MYC and FOXO1, which regulate zonal recycling and differentiation. As lupus progressed, decreased mutational frequency and repertoire diversity were associated with reduced responsiveness to CD40 signaling, despite accumulation of plasma cells. Collectively, these findings suggest that lupus disease progression coincides with an intrinsic defect in LZ B cell signaling, altering the zonal recycling, selection, and differentiation of autoreactive B cells. Competing Interests: Declaration of interests The authors report no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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