Pre-activation of follicular B cells in old mice generates a hyper-response during germinal center reaction.
نویسندگان
چکیده
Abstract Immune cells acquire a variety of defects that accumulate overtime in process known as Immunosenescence. To study any innate B lymphocytes may during aging, we have developed an adoptive transfer system using follicular from young (FO Y, 8–12 weeks) and old O, >22 mo.) mice into μMT cell-deficient mouse. This model reveals FO Ocells, compared to their counterparts, produce higher amount activated germinal center (GC) the presence common antigen NP-CGG after 14 days immunization. However, these do not antigen-specific antibodies while showing significant decrease NP+ λ+ antigen-specificity. this change phenotype further, performed single cell RNA sequencing both populations naïve, day GC cells. Comparison naïve by PCA showed only minor differences between populations. Interestingly, Ccr6is being upregulated Ocells but has decreased expression population GCs. suggests are pre-activated before encounter. Analysis immunoglobulin repertoire also use canonical NP-specific IgH V-gene 1–72 fail include CDR2 W33L mutation is increase antibody affinity 10-fold. Taken together, findings show hyper-responsive cause lack proper selection maturation reaction. research was supported part Intramural Research Program NIH, National Institute on Aging.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.83.12