Abstract
Antibody secreting cells (ASCs) are terminally differentiated cells of the humoral immune response and must adapt morphologically, transcriptionally, and metabolically to maintain high-rates of antibody (Ab) secretion. ASCs differentiate from activated B cells in lymph nodes and transiently circulate in the blood. Most of the circulating ASCs undergo apoptosis, but a small fraction of early ASCs migrate to the bone marrow (BM) and eventually mature into long-lived plasma cells (LLPCs). LLPC survival is controlled both intrinsically and extrinsically. Their differentiation and maintenance programs are governed by many intrinsic mechanisms involving anti-apoptosis, autophagy, and metabolism. The extrinsic factors involved in LLPC generation include BM stromal cells, cytokines, and chemokines, such as APRIL, IL-6, and CXCL12. In humans, the BM CD19−CD38hiCD138+ ASC subset is the main repository of LLPCs, and our recent development of an in vitro BM mimic provides essential tools to study environmental cues that support LLPC survival and the critical molecular mechanisms of maturation from early minted blood ASCs to LLPCs. In this review, we summarize the evidence of LLPC generation and maintenance and provide novel paradigms of LLPC maturation.
Highlights
A key aspect of the adaptive immune response is the rapid production of high-affinity antibodies (Abs)
The bimodal characteristics of serum Ab decay after infection or long-lived vaccines suggests that the large initial burst of Antibody secreting cells (ASCs) is responsible for the peak of serum Ab titers and the secondary decay is due to ASCs with longer half-lives [11]
We focus on the molecular and cellular processes involved in the adaptation of ASCs after exiting the germinal center (GC) into the medullary cords and efferent lymphatics and upon entering the blood, and eventually the bone marrow (BM) niche (Figure 1D)
Summary
A key aspect of the adaptive immune response is the rapid production of high-affinity antibodies (Abs). This antibody production is the function of an antibody secreting cell (ASC), which arises from naïve (or memory) B cells as they encounter antigen, activate, proliferate, and differentiate. Differentiated ASCs subsequently egress out of lymph nodes and circulate in the blood (Figure 1B). Despite their critical function, ASCs are rare and comprise of no more than ∼0.01–1% of the total cellularity in the circulation and lymphoid tissues. The bimodal characteristics of serum Ab decay after infection or long-lived vaccines suggests that the large initial burst of ASCs is responsible for the peak of serum Ab titers and the secondary decay is due to ASCs with longer half-lives [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
