LBH deficiency influences the therapeutic effects of regulatory B cells through the regulation of IL-10 production via the Rap1 pathway

Regulatory B cells (Bregs) are immune cells that affect the autoimmune response by producing interleukin (IL)-10, but the molecular mechanism affecting Breg differentiation and IL-10 production is not clear. Our study found that mice with limb bud and limb-bud and heart (LBH) gene deficiency in dextran sulfate sodium (DSS)-induced colitis showed severe colitis but exhibited an increase in Bregs in mesenteric lymph nodes and the spleen. LBH deficiency increased IL-10 production and expression of the surface molecule CD24 in B cells. Mechanistically, Ras-proximate-1 (Rap1) signaling pathway activation in LBH-deleted B cells and simultaneous inhibition of Rap 1 activation or extracellular signal-related kinase (ERK) phosphorylation reduced Breg differentiation among B cells. Furthermore, LBH deficient B cells showed a more significant therapeutic effect on DSS-induced colitis. Taken together, the results of this study revealed the mechanism by which LBH affects IL-10 production during Breg differentiation and that LBH deficiency enhanced the therapeutic efficacy of B cells for DSS-induced colitis.