Abstract

Abstract B-1a cells arise predominately during fetal development, and their persistence throughout adult life is maintained through self-renewal. These cells are essential for immediate protection from S. pneumoniae infection. The unique ability of fetal derived B-1a cells to provide protection against S. pneumoniae is attributed to their spontaneously secreted natural IgM, which is germline-like due to minimal insertion of N-region additions and little somatic hypermutation. The B-1a cell pool is also maintained by B-1 cell progenitors found in the adult bone marrow. We reported these bone marrow derived (BMD) B-1a cells are functionally and phenotypically similar to native B-1a cells; however, BMD B-1a cells contain an increased number of N-region additions in their natural IgM as compared to native B-1a cells. Natural IgM derived from native B-1a cells in aged mice also contains more N-region additions. We show an increase in N-region addition in mice 6 months to 24 months of age. This suggests the repertoire of B-1a derived natural IgM changes with age, and the adult B-1a cell pool is not a closed system. We hypothesized the level of natural IgM protection changes with age as a result of repertoire alterations to the B-1a cell pool over time. We found the natural IgM from aged mice is less effective at protection from S. pneumoniae infection. Data presented here suggest age related changes of natural IgM can lead to less effective initial protection against infection.

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