SpiB regulates the expression of B-cell-related genes and increases the longevity of memory B cells
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Published:2023-10-27
Issue:
Volume:14
Page:
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ISSN:1664-3224
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Container-title:Frontiers in Immunology
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language:
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Short-container-title:Front. Immunol.
Author:
Horiuchi Shu,Koike Takuya,Takebuchi Hirofumi,Hoshino Katsuaki,Sasaki Izumi,Fukuda-Ohta Yuri,Kaisho Tsuneyasu,Kitamura Daisuke
Abstract
Generation of memory B cells is one of the key features of adaptive immunity as they respond rapidly to re-exposure to the antigen and generate functional antibodies. Although the functions of memory B cells are becoming clearer, the regulation of memory B cell generation and maintenance is still not well understood. Here we found that transcription factor SpiB is expressed in some germinal center (GC) B cells and memory B cells and participates in the maintenance of memory B cells. Overexpression and knockdown analyses revealed that SpiB suppresses plasma cell differentiation by suppressing the expression of Blimp1 while inducing Bach2 in the in-vitro-induced germinal center B (iGB) cell culture system, and that SpiB facilitates in-vivo appearance of memory-like B cells derived from the iGB cells. Further analysis in IgG1+ cell-specific SpiB conditional knockout (cKO) mice showed that function of SpiB is critical for the generation of late memory B cells but not early memory B cells or GC B cells. Gene expression analysis suggested that SpiB-dependent suppression of plasma cell differentiation is independent of the expression of Bach2. We further revealed that SpiB upregulates anti-apoptosis and autophagy genes to control the survival of memory B cells. These findings indicate the function of SpiB in the generation of long-lasting memory B cells to maintain humoral memory.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Publisher
Frontiers Media SA
Subject
Immunology,Immunology and Allergy