The effects of an aged microenvironment on mature B cell homing and distribution of CXCL13 (82.13)

Abstract The splenic architecture in many aged mice appears disrupted, with some similarities to the disorganization observed in mice lacking the chemokine, CXCL13. Particularly, small follicles and germinal centers are reported and the marginal zone (MZ) appears disrupted. Changes in the proportion of B cell subsets in bone marrow (BM) and secondary lymphoid tissue suggest that migration patterns may be altered. We tested the ability of young splenic B cells to migrate in an aged microenvironment. Of note, donor B cells significantly increased homing to BM in an old host. Nonetheless, similar numbers of donor follicular B cells were found in the spleens and localized to the follicles of aged vs. young recipients. However, fewer donor MZ B cells migrated into aged spleens. Unexpectedly, CXCL13 protein levels, assessed by ELISA, were greater in spleens from aged mice, but differences were apparent in the histological distribution of CXCL13 protein between young and old spleens. In old spleens, CXCL13 was unevenly distributed, concentrated in patches throughout the follicles, and reduced or absent at the follicular edge. The data suggest that CXCL13 expression may be dysregulated in aged mice. While the consequences of changes in CXCL13 distribution are under investigation, it appears not to directly affect follicular B cell migration and may have more impact on MZ B cells. NIH R01AG013874 and CCC Faculty Development Grant.