Advances in Plasma Cells in Health and Disease

Protective plasma cells (PCs) arise following infection and vaccination, and long-lived plasma cells (LLPCs) provide humoral protection for a lifetime. PCs are the resting, non-proliferative, terminally differentiated effectors of B cells that secrete protective antibodies decades following antigen encounter. In the blood, early antibody secreting cells (ASCs) eventually mature into LLPCs, but the specific molecular programs regulating this maturation process remain elusive. The phenotype of human LLPCs is currently defined as a CD19negCD138+CD38hi compartment. However, even within this well-defined population, these cells are likely to be heterogeneous. Size, ribosomal content and the metabolic status of the LLPC remain important questions. Their functional capacity to constitutively secrete antibodies has also never been challenged. Similarly, whether particular ASC subsets have differential secretion rates and whether they correlate with their lifespan, is currently unknown. The specific location of LLPCs within the bone marrow appears to play a fundamental role in the generation and/or maintenance of these cells,and neighboring cells appear to provide important survival signals. Whether these effects on PCs are mediated via intra-cellular crosstalk; via direct cell-cell contact and/or by paracrine effects remains poorly understood. Thus, many questions remain regarding the mechanisms involved in the generation and maintenance of protective PCs.

Interestingly, not all PCs are protective. In human disease, aberrations in PC generation and maintenance can result in pathogenic PCs. Autoimmune diseases are models of alterations in normal PC generation while PC dyscrasias are examples of enhanced proliferation and survival of transformed PCs. Tolerance is broken in autoimmune diseases, such as systemic lupus erythematosus (SLE) and pemphigus vulgaris, and PCs that secrete antibodies to self-antigens become pathogenic, targeting cellular factors that subsequently result in organ damage. Multiple Myeloma is a PC-derived malignancy characterized by the clonal expansion of PCs, resulting in (i) increased frequency of infections; (ii) lytic bone lesions; (iii) hypercalemia and death. Similar to LLPCs, the role of the bone marrow niche has been shown to provide important mediators for the survival of these malignant PCs. However, little is known about the precise mechanisms of how pathogenic PCs are produced and sustained, and how they compare to healthy protective PCs.

In this Research Topic, we aim to gather a series of up-to-date and novel findings on the advances in plasma cells in health and disease. We welcome investigators in the field of PC biology to submit Original Research and Review articles encompassing, but not limited to, the following topics:

1. The role of the Germinal Center and BCR signaling strength in modulating LLPC development and generation.
2. The potential roles of T-bet in LLPC generation.
3. The requirement of the GC by memory B cells for PC generation.
4. Metabolic changes in PCs.
5. The role of location in determining PC survival: cells, ligands, and other environmental factors.
6. Transcriptional profiles of short versus long-lived plasma cells.
7. Alterations in the epigenetic landscape of early ASCs and LLPCs.
8. VH repertoire analysis of protective and pathogeneic plasma cells.
9. Maturation profiles of human blood ASC to LLPC.
10. Are LLPCs invariably post-mitotic?
11. Differences and similarities between normal and neoplastic PCs (MGUS, AL, Multiple Myeloma).
12. Mechanisms of autoimmune plasma cell generation and maintenance.
13. Comparisons of blood ASC in health and disease.
14. Comparisons of bone marrow plasma cells in health and disease.
15. Mechanisms of mucosal plasma cell generaton.