B Cells Reside in the Healthy Murine Retina and are Altered by Lack of IgM 2245387

Abstract Introduction The retina, the central nervous tissue responsible for vision, undergoes functional decline with aging contributing to onset of many diseases. Preserving vision requires a better understanding of how retinal homeostasis is maintained. While the retina has historically been considered immune privileged, recent evidence indicates that ocular tolerance arises from strong, active immune regulation rather than immune system absence. Building on our prior findings that secreted IgM is required for proper retinal homeostasis through aging, we investigated whether retinal B cells contribute to this regulation. Methods Using uS-/- mice (no secreted IgM) and their wild-type counterparts, we collected lymphocytes from retinal extracts separating the vasculated choroid/sclera from the neural and non-neural retina. B cells were analyzed for phenotype by multiparameter flow cytometry, response to LPS in culture, and repertoire by single cell V(D)J sequencing. Results Phenotyping revealed a distinct B cell population that resided primarily in the retinal pigment epithelium layer (RPE), not the choroid/sclera or the neural retina. To our knowledge, this represents the first evidence of resident B cells in the healthy retina. In uS-/- mice a higher percent of these cells displayed CD80, indicating a larger proportion of activated cells than those found in the WT mice. Sorted CD19+ B cells from the RPE responded to LPS stimulation in vitro, demonstrating functional antibody production; while WT CD19+ cells preferentially secreted IgM, us-/- CD19+ cells produced IgG. Single cell sequencing data showed that the CD19+ RPE B cell repertoire shifts with both age and secreted IgM deficiency. Conclusion Together, these results identify a novel population of resident B cells in the RPE and demonstrate that secreted IgM regulates their activation state and repertoire. This work reveals an unrecognized role for B cells in retinal homeostasis and provides new insight into immune regulation within the central nervous system. Funding Source NIH NIAID F32AI174673-01A1 Topic Categories Neuroimmunology (NEUR)