Cellular Basis of Antibody Maintenance: Heterogeneity of the Bone Marrow Plasma Cell Pool

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Doctor of Philosophy (PhD)
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B cells
Bone Marrow
cell differentiation
Plasma Cells
Allergy and Immunology
Immunology and Infectious Disease
Medical Immunology
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Plasma cells are the immune system cells responsible for producing antibodies, the key mediators of protective humoral immunity. Long-lived plasma cells (PC) are thought to be responsible for maintaining antibody titers and are believed to populate unique survival niches in the bone marrow (BM). Current models predict that bone marrow plasma cells (BM PC) consist chiefly of long-lived, slowly renewing cells. In chapter 2, we show the turnover rate of the BM PC pool to be much higher than predicted by these models; in fact, more than 50% of BM PC exhibit characteristics of recently formed PC. Intriguingly, these B220+ PC do not appear to be cycling and are depleted upon ablation of peripheral B cell pools. In chapter 3, we extend our studies to antigen-induced responses. We find that very long-term maintenance of the antigen-specific BM PC pool is dependent on a CD40-independent B cell precursor. Despite the rapid turnover rate exhibited by B220+ BM PC, antigen-induced antibody secreting cells are found within this population for more than 100 days post-immunization. These cells secrete exclusively low affinity, unswitched, κ type antibodies in sharp contrast to the high affinity, isotype switched cells found within the slowly renewing BM PC pool. Finally, we identify a population of rapidly renewing memory B cells that appear to be the precursors of the B220+ BM PC. Together these data suggest that BM niches are continuously repopulated by newly generated plasma cells long after antigenic exposure and identify the memory B cell precursors of BM PC.

David Allman
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