| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 38, Iss 4, Pp 110200- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2021.110200 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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