Sex Chromosomes and Gonadal Hormones Contribute to B Cell Antibody Responses in Aging and Alzheimer's Disease

Abstract

It is increasingly appreciated that B cell populations in the brain shift during aging and Alzheimer's Disease (AD), contributing to neuroinflammation and cognitive decline. Though the underlying mechanisms remain unclear, biological sex is likely a key regulator since differences in B cell antibody responses are one of the most well conserved sex differences in immunology. Sex differences in B cell subtypes and antibody classes are significant because they drive sexually dimorphic immune responses and subsequent disease susceptibility. Despite extensive work evaluating the effects of gonadal hormones on B cells, the effects of aging and AD pathology, and the contributions of sex chromosomes are understudied. We evaluated B cell subtypes in the brain and bloodstream in both adult and 5xFAD mice via flow cytometry and antibody levels in the cortical brain region of both groups via ELISAs. We found sex differences mediated by both sex chromosomes and the gonadal hormone environment; these differences were primarily involved in antibody class-switching.