Research Day
SEX INFLUENCES ORGAN-SPECIFIC DIFFERENCES IN THE PRODUCTION AND ACTIVATION OF PLASMABLASTS AND PLASMA CELLS
Document Type
Abstract
Date
2021
Abstract
Sex dichotomies exist regarding both physiological immune responses and pathological autoimmune responses. However, very little information exists as to how sex patterns antibody-secreting plasmablasts (PBs) and plasma cells (PCs). Using the Prdm1-enhanced yellow fluorescent (eYFP) reporter mouse strain, we compared the prevalence of PBs and PCs in the bone marrow (BM), spleen (SPL) and thymus (THY) of young (3 months old) female and male mice. While PB/PC generation was equivalent in the BM and SPL of both sexes, the female THY had significantly increased percentages and numbers of both PBs and PCs when compared to males. This correlated with the overall increase in thymopoiesis present in females. Characterization of THY PBs/PCs demonstrated increased expression of canonical activation markers such as CD69 and MHC II when compared to their BM and SPL counterparts. In some aspects, these differences were sex-based in origin. Anti-CD45 intravenous antibody labeling suggested that THY PBs/PCs were locally generated and not THY immigrants. As such, female THY demonstrated increased numbers of a germinal center B (GCB) cell-like population expressing both GL7 and CD95(Fas). THY B cells have been previously shown to participate in the regulation of T cell selection and we hypothesized that THY PBs/PCs would be generated in a T cell dependent manner. Indeed, administration of anti-CD40L blocking antibodies ablated THY GCB, PB and to some extent PC production. In summary, female mice are skewed towards increased THY PB/PC generation. The production of these cells happens locally and is dependent on CD40L-based T cell interactions.