Objective-Mesenchymal stem cells (MSCs) have been shown to possess immunomodulatory properties on a diverse array of immune cell lineages. However, their effect on B-lymphocytes has remained unclear. We investigated the effect of MSCs on B cell modulation with a special emphasis on gene regulation mediated by MSC humoral factors.Methods-MSCs were isolated from C57BL/6 bone marrow and expanded in culture. Splenic B cells were purified using anti-CD43 antibody and immunomagnetic beads. B cells and MSCs were co-cultured in separate compartments in a transwell system. For B cell stimulation, lipopolysaccharide (LPS) was used in vitro and T-dependent and T-independent antigens were used in vivo.Results-In MSC co-cultures, LPS-stimulated B cell proliferation was suppressed, CD138 + cell percentage decreased, and the number of apoptotic CD138 + cells decreased. In the B/MSC co-culture, the IgM + cell percentage was higher and the IgM amount released in the medium was lower than in the control. The Blimp-1 mRNA expression in the co-culture was suppressed throughout the 3 day culture period. Conditioned media derived from MSC cultures prevented the terminal differentiation of B cells in vitro and significantly suppressed the antigen specific IgM and IgG1 secretion in mice immunized with T cell-independent as well as T cell-dependent antigens in vivo. Conclusion-Resultsindicate that humoral factor(s) released by MSCs exert a suppressive effect on the B cell terminal differentiation. The suppression may be mediated through inhibition of Blimp-1 expression, but the nature of the factor(s) is yet to be determined.

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Naïve T cells proliferate and differentiate into memory cells after antigenic stimulation or in a lymphopenic environment. We showed here transient increases in memory phenotype CD8+ T cell numbers in the lymphopenic environment of spleens of very young mice. The magnitude of the increase correlated with Bcl-6 expression in the T cells. Bcl-6 controlled the generation and maintenance of antigen-specific memory phenotype CD8+ T cells in the spleens of immunized mice. These data suggest that Bcl-6, which is essential for memory B cell development in germinal centers, is a key molecule for the establishment not only of memory T cells but also of the peripheral T cell compartment in infancy.

After immunization with T cell-dependent antigens, the high-affinity B cells selected in germinal centers differentiate into memory B cells or long-lived antibody-forming cells. However, a role for germinal centers in development of these B lineage cells is still controversial. We show here that Bcl6-deficient B cells, which cannot develop germinal centers, differentiated into IgM and IgG1 memory B cells in the spleen but barely differentiated into long-lived IgG1 antibody-forming cells in the bone marrow. Mutation in the V-heavy gene was null in these memory B cells. Therefore, Bcl6 and germinal center formation are essential for somatic hypermutation, and generation of memory B cells can occur independently of germinal center formation, somatic hypermutation, and Ig class switching.

Intraoperative use of fibrin glue following distal pancreatectomy could prevent pancreatic fistula formation. This method was feasible, safe, and reliable and will complement other prophylactic methods.