Mechanisms governing plasma cell selection and longevity

All vaccines in routine use primarily confer protection by inducing antibodies, however the durability of protection varies based on the vaccine platform.

Long-lived plasma cells in the bone marrow are terminally differentiated B cells that constitutively secrete antibodies into the circulation. Their life span varies from months to decades, but the mechanisms regulating their longevity are not well understood.

Whereas B cells carrying high-affinity B cell receptors (BCRs) are enriched in the plasma cell compartment, plasma cell selection is not solely governed by the BCR affinity. Moreover, immunogen structure itself and the innate immune stimulation appear to modulate the plasma cell survival.

Deciphering the molecular pathways that shape selection and promote survival of plasma cells could be used to support development of vaccines and other therapies targeting antibody-secreting cells. In the present study, we will employ novel transgenic mouse models developed by Dr. Nussenzweig’s group which enable lineage tracing of plasma cells over extended periods of time.

Through a combination of immunological, molecular, and biophysical approaches, we will seek to understand how plasma cells are selected during the germinal center reaction, and what contributes to their survival in the bone marrow niche.

Together, this study will be used to gain mechanistic insight into plasma cell biology and can provide novel pathways to target for induction of durable antibody responses.