Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.00965
Keywords
long-lived plasma cells (LLPC); plasma cell survival; plasma cell niche; plasma cell function; humoral responses
Categories
Funding
- National Institutes of Health (NIH) [R01CA121044, T32CA085183]
- National Cancer Institute (NCI) [R01AI100157]
- National Institute of Allergy and Infectious Diseases (NIAID)
Ask authors/readers for more resources
Durable humoral immunity is dependent upon the generation of antigen-specific antibody titers, produced by non-proliferating bone marrow resident long-lived plasma cells (LLPC). Longevity is the hallmark of LLPC, but why and how they survive and function for years after antigen exposure is only beginning to be understood. LLPC are not intrinsically long-lived; they require continuous signals from the LLPC niche to survive. Signals unique to LLPC survival (vs. PC survival in general) most notably include those that upregulate the anti-apoptotic factor Mcl-1 and activation of the CD28 receptor expressed on LLPC. Other potential factors include expression of BCMA, upregulation of the transcription factor ZBTB20, and upregulation of the enzyme ENPP1. Metabolic fitness is another key component of LLPC longevity, facilitating the diversion of glucose to generate pyruvate during times of stress to facilitate long term survival. A third major component of LLPC survival is the microenvironment/LLPC niche itself. Cellular partners such as stromal cells, dendritic cells, and T regulatory cells establish a niche for LLPC and drive survival signaling by expressing ligands such as CD80/CD86 for CD28 and producing soluble and stromal factors that contribute to LLPC longevity. These findings have led to the current paradigm wherein both intrinsic and extrinsic mechanisms are required for the survival of LLPC. Here we outline this diverse network of signals and highlight the mechanisms thought to regulate and promote the survival of LLPC. Understanding this network of signals has direct implications in increasing our basic understanding of plasma cell biology, but also in vaccine and therapeutic drug development to address the pathologies that can arise from this subset.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available