DCs activated by TLR ligands initiate type 1 immune responses (see green DC). The activated DCs produce IL-12 and present antigen to naïve T cells, facilitating their differentiation into Th1 effectors. Naïve FO B cells also respond to the TLR ligands and the DC-derived IL-12 and differentiate into IFNγ and IL-12 producing Be-1 cells. The IL-12 and IFNγ producing Be-1 cells can also present antigen to the naïve T cells and promote Th1 differentiation. Th1 effectors form cognate interactions with new cohorts of naïve FO B cells and provide co-stimulatory signals and IFNγ which promote the differentiation of the naïve FO B cells into IFNγ and IL-12 producing Be-1 cells. These cytokine producing and antigen presenting Be-1 cells can subsequently prime new naïve T cells and facilitate their differentiation into Th1 cells. Thus, Be-1 cells can initiate a positive feedback loop that amplifies and maintains Th1 responses. However, naïve MZ and T2 B cells (and potentially FO B) can also respond to signals delivered by TLR ligands, CD40 crosslinking or antigen and differentiate into IL-10 producing regulatory B cells. The IL-10 producing Bregs can block IFNγ production by Th1 effectors and reduce the inflammatory response. It is also possible that the IL-10 producing Bregs block the Th1 dependent differentiation of naïve B cells into Be-1 cells and short circuit the Be-1/Th1 amplification network.

DCs activated by allergens or antigens derived from helminths initiate type 2 immune responses (see green DC). The activated DCs present antigen to naïve T cells, facilitating their differentiation into Th2 effectors. Th2 effectors form cognate interactions with naïve FO B cells and provide CD154 and IL-4, promoting the differentiation of the naïve FO B cells into IL-4, IL-13 and IL-2 producing Be-2 cells. These cytokine-producing and antigen-presenting Be-2 cells can subsequently prime new naïve T cells and facilitate their differentiation into Th2 cells. Thus, Be-2 cells can initiate a positive feedback loop that amplifies and maintains Th2 responses. However, naïve MZ B cells (and potentially FO B) can also respond to signals delivered by TLR ligands, CD40 crosslinking or antigen and differentiate into IL-10 producing regulatory B cells. The IL-10 producing Bregs can block IL-4 production by Th2 effectors and reduce the inflammatory response. It is also possible that the IL-10 producing Bregs block the Th2 dependent differentiation of naïve B cells into Be-2 cells and short circuit the Be-2/Th2 amplification network.

TLR ligands initiate immune responses in neonates by activating B1a B cells and DCs. IL-10 produced by the TLR-activated neonatal Bregs blocks production of IL-12 by the TLR-activated DCs. This reduction in IL-12 production by the DCs facilitates the priming of Th2 cells rather than Th1 cells. Type I interferons produced by the TLR activated DCs (particularly plasmacytoid DCs) facilitates IL-10 production by the B cells and further enhances the suppression of the Th1 response to the TLR ligands. B cells from secondary lymphoid organs of adult animals, which are primarily composed of B2 FO B cells, make only small quantities of IL-10 in response to TLR ligands and cannot block TLR-induced Th1 responses.