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Regulation of the BCR signalosome by the class II peptide editor, H2-M, affects the development and repertoire of innate-like B cells

Regulation of the BCR signalosome by the class II peptide editor, H2-M, affects the development and repertoire of innate-like B cells

Authors :
Debopam Ghosh
Tho D. Pham
Padma P. Nanaware
Deepanwita Sengupta
Lital N. Adler
Caiyun G. Li
Xiao He
Mary E. O'Mara
Aaron B. Kantor
Khoa D. Nguyen
Yang Yang
Laurence C. Eisenlohr
Peter E. Jensen
Leonore A. Herzenberg
Lawrence J. Stern
Scott D. Boyd
Eliver E.B. Ghosn
Elizabeth D. Mellins
Source :
Cell Reports, Vol 38, Iss 4, Pp 110200- (2022)
Publication Year :
2022
Publisher :
Elsevier, 2022.

Abstract

Summary: The non-classical Major Histocompatibility Complex class II (MHCII) protein, H2-M, edits peptides bound to conventional MHCII in favor of stable peptide/MHCII (p/MHCII) complexes. Here, we show that H2-M deficiency affects B-1 cell survival, reduces cell renewal capacity, and alters immunoglobulin repertoire, allowing for the selection of cells specific for highly abundant epitopes, but not low-frequency epitopes. H2-M-deficient B-1 cells have shorter CDR3 length, higher content of positively charged amino acids, shorter junctional regions, less mutation frequency, and a skewed clonal distribution. Mechanistically, H2-M loss reduces plasma membrane p/MHCII association with B cell receptors (BCR) on B-1 cells and diminishes integrated BCR signal strength, a key determinant of B-1 cell selection, maturation, and maintenance. Thus, H2-M:MHCII interaction serves as a cell-intrinsic regulator of BCR signaling and influences the selection of the B-1 cell clonal repertoire.

Details

Language :
English
ISSN :
22111247
Volume :
38
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.bd96043bdd1c4fd6babe806d58bfbeb0
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2021.110200