The formation and maintenance of long-lived plasma cells in T-independent and T-dependent immune responses

Antibodies play protective roles in host defense, and can cause disease when specific for self-antigens. Long-lived plasma cells (PCs) are thought to maintain protection for a lifetime, but the signals required for their induction and survival remain unclear. In Chapter 2, the T-independent (TI) antigen NP-LPS is revealed to induce long-lived plasma cells. TI plasma cells, conventionally thought to undergo apoptosis within days of their generation, persist for months after a single inoculation with NP-LPS, and are maintained in the bone marrow in the complete absence of T cells. Moreover, long-lived plasma cells are shown to be generated exceptionally early during a T-dependent (TD) immune response, well before the canonical germinal center pathway takes hold. Chapter 3 extends on these findings and addresses the cellular and molecular requirements for the generation and maintenance of TD and TI plasma cells. The requirement of BLyS family receptors BCMA and TACI and the role of eosinophils is examined. Surprisingly, mice genetically deficient in mature eosinophils, regardless of their genetic background, exhibit a complete loss in mature eosinophils but have normal numbers of total and high-affinity bone marrow plasma cells. Prolonged depletion of eosinophils with anti-Siglec-F in wildtype mice also did not perturb plasma cell numbers. Altogether, these data argue that B cells gain the competence to become long-lived cells exceptionally early during immune responses, well before a germinal center response takes hold, and to antigens long thought to produce only transient antibody responses. Further, TI plasma cells do not require T cells for their induction or maintenance and rely on alternative cellular and molecular signals for their survival compared to TD plasma cells, redefining the features of a 'specialized niche' for plasma cells in the bone marrow. These findings make fundamental revisions to the current and widely-cited model of humoral immunity.