Age-Related Changes in Antigen-Specific Natural Antibodies are Influenced by Sex

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B815
Abstract ID: 5404

Presenting Author:
Nichol E Holodick , Associate Professor at Western Michigan Univ. Homer Stryker MD Sch. of Med.

Abstract:

Natural antibodies (NAbs) produced by B1 cells maintain tissue homeostasis, control inflammation, and provide immediate protection from infection. NAbs recognizing epitopes such as phosphatidylcholine (PtC) are essential in protection against bacterial sepsis. B1a cell-derived NAbs have a unique germline-like structure, which is critical for providing protection against infection. We have shown that serum antibodies from aged female mice maintain protection against pneumococcal infection, whereas those from male mice do not. Here, we show aged female mice have significantly more splenic PtC+ B1a cells and PtC-specific serum IgM than aged male mice. We find age- and sex-related repertoire differences when comparing single cell B cell receptor sequencing results of PtC+ B1a cells. Splenic PtC+ B1a cells in aged females retain germline configuration, while aged males do not. Maintenance of PtC+ B1a cells is dependent on nucleic acid-sensing toll-like receptors (TLRs). As such, we analyzed the serum of aged mice for cell-free nucleic acids and found that aged females have significantly more than aged males. Our results suggest the antigenic milieu differs between aged males and females, leading to differential selection of antigen-specific B1 cells over time. Further elucidation of how biological sex influences the maintenance of B1 cells within the aging environment will be essential to appreciate sex and age-related disparities in the susceptibility to bacterial infection.