Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-κB p50-deficient mice

Mice (2 months of age) deficient in p50 (p50-/-) had small numbers of MZ B cells, as determined by cell surface phenotype and localization in the splenic MZ. These cells bound high levels of IgM-IC both in vivo and in vitro. Subsequent to the binding of IgM-IC by the MZ B cells in p50-/- mice, small amounts of IgM-IC were found localized on FDCs, suggesting that the MZ B cells retained their ability to transport these complexes into splenic follicles. Strikingly, MZ B cells accumulated with age in p50-/- mice. By 6 months of age, p50-/- mice contained normal numbers of these cells as defined by CD21/CD23 profile and high level expression of CD1d, CD9, and IgM, and by their positioning around the marginal sinus. However, FDCs from these older p50-/- mice exhibited a reduced capacity to trap IgM-IC and retain complement components.These results demonstrate that while the p50 component of the NF-κB transcription complex plays an important role in the early development of MZ B cells, MZ B cells can develop and accumulate in mice lacking this protein. These results highlight the interface between genetic deficiencies and age, and suggest that different transcription factors may play distinct roles in the development and maintenance of cell populations at different ages.Secreted IgM antibodies play important roles in the initial phases of humoral immune responses. Unlike other antibody isotypes, secreted IgM uniquely functions as an adjuvant, promoting primary antibody responses to sub-immunogenic doses of T-dependent antigens [1-7]. The adjuvanticity of IgM is completely dependent on an intact complement system [7-9]. While mice deficient in secreted IgM make protective antibody responses to pathogens, these responses are delayed compared to the immune response of IgM sufficient mice [10-13] Interestingly, pathogens more readily disseminate into vital organs in secreted IgM-deficient mice, rather than concentrate them into secondary lymphoid organs [14]. This suggests th