TLR signaling in human CD27⁺IgM⁺IgD⁺ B cells. (A) Differentiation scheme of CD27⁺IgM⁺IgD⁺ and CD27⁺IgD- memory B cells. Human CD27⁺IgM⁺IgD⁺ B cells in the splenic marginal zone are thought to derive from T cell–independent responses and able to circulate in peripheral blood. CD27⁺IgD-IgM⁺, IgA⁺ or IgG⁺ memory B cells and at least part of the CD27⁺IgM⁺IgD⁺ B cells derived from T cell–dependent germinal center responses. (B) Scheme of human TLRs and critical signaling molecules. Weller et al demonstrated that the presumed marginal zone-derived CD27⁺IgM⁺IgD⁺ B cells depend on MyD88, TIRAP, and IRAK4 (red), but not on TLR3, UNC93B, or TRIF (blue). TLRs form homodimers, except for TLR1 and TLR6 which function as heterodimers with TLR2. TLR10 potentially functions as homodimer or as heterodimer with TLR1 or TLR2. Professional illustration by Marie Dauenheimer.