Bone Marrow Mesenchymal Stem Cells Enhance the Differentiation of Human Switched Memory B Lymphocytes into Plasma Cells in Serum-Free Medium

Abstract

The differentiation of human B lymphocytes into plasma cells is one of the most stirring questions with regard to adaptive immunity. However, the terminal differentiation and survival of plasma cells are still topics with much to be discovered, especially when targeting switched memory B lymphocytes. Plasma cells can migrate to the bone marrow in response to a CXCL12 gradient and survive for several years while secreting antibodies. In this study, we aimed to get closer to niches favoring plasma cell survival. We tested low oxygen concentrations and coculture with mesenchymal stem cells (MSC) from human bone marrow. Besides, all cultures were performed using an animal protein-free medium. Overall, our model enables the generation of high proportions of CD38+CD138+CD31+ plasma cells (≥50%) when CD40-activated switched memory B lymphocytes were cultured in direct contact with mesenchymal stem cells. In these cultures, the secretion of CXCL12 and TGF-β, usually found in the bone marrow, was linked to the presence of MSC. The level of oxygen appeared less impactful than the contact with MSC. This study shows for the first time that expanded switched memory B lymphocytes can be differentiated into plasma cells using exclusively a serum-free medium.

Leukoreduction system chambers are a reliable cellular source for the manufacturing of T‐cell therapeutics

“…The LRSC and blood sample were stored at room temperature and processed within 24 hours. The isolation of PBMCs from the LRSC was performed as previously described . Briefly, individual LRSCs were back‐flushed using 40 mL of Hank's balanced salt solution (Gilco) supplemented with 10% anticoagulant citrate dextrose solution (USP formula A, Fenwal).…”

“…The isolation of PBMCs from the LRSC was performed as previously described. 6,35 Briefly, individual LRSCs were back-flushed using 40 mL of Hank's balanced salt solution (Gilco) supplemented with 10% anticoagulant citrate dextrose solution (USP formula A, Fenwal). The recovered PBMCs were isolated by centrifugation on a sterile medium for isolation of lymphocytes as recommended by the manufacturer (Ficoll-Paque Plus, GE Healthcare).…”

Remembrance of Things Past: Long-Term B Cell Memory After Infection and Vaccination

“…Mesenchymal stromal cells (MSC) in the human bone marrow microenvironment provide factors that support LLPC survival (95–97). Cytokines of the TNF superfamily (BAFF, APRIL and TNF-α), IL-6 family, CD80/CD86, CD44 binding to hyaluronic acid, and VLA-4 binding to VCAM-1/fibronectin promote survival of plasma cells.…”

SOCS1 Regulates the Immunomodulatory Roles of MSCs on B Cells

“…In addition, it has been found in recent years that MSCs have immunomodulatory capacity and the potential to treat a variety of inflammation-related diseases (1)(2)(3). Currently, studies on immune regulation of T cells by MSCs have been extensively provided (1,4,5), but reports on the effects of MSCs on B cell function are rare and present conflicting data (2,(6)(7)(8)(9)(10)(11). Some studies have reported that MSCs can promote B cell proliferation, activation, differentiation and antibody secretion (7-9, 12, 13), while others have shown opposite effects (10,11,(14)(15)(16)(17)(18).…”

“…Currently, studies on immune regulation of T cells by MSCs have been extensively provided ( 1 , 4 , 5 ), but reports on the effects of MSCs on B cell function are rare and present conflicting data ( 2 , 6 - 11 ). Some studies have reported that MSCs can promote B cell proliferation, activation, differentiation and antibody secretion ( 7 - 9 , 12 , 13 ), while others have shown opposite effects ( 10 , 11 , 14 - 18 ). The main reason for this contradiction is that the immune regulation mechanism of MSCs on B cells remains unclear.…”