Toll-like receptors and B cells: functions and mechanisms

Abstract

Numerous reports have described Toll-like receptor (TLR) functions in myeloid cells such as dendritic cells (DCs) and macrophages, but relatively fewer studies have examined TLR responses in B lymphocytes. B cells express a wide variety of TLRs and are highly activated after TLR ligation, leading to enhancements in B cell survival, surface molecule expression, cytokine and antibody production, and antigen presentation. During an immune response, B cells can receive signals through TLRs as well as the B cell antigen receptor (BCR) and/or CD40. TLR ligation synergizes with signals through these receptors and augments both innate and adaptive immune functions of B lymphocytes. Additionally, targeting B cell TLRs may provide new therapies against certain types of cancer as well as autoimmune diseases. Here, we summarize TLR expression and contributions to both normal and pathogenic functions in mouse and human B cells.

Roles of Toll-Like Receptors 2 and 4 in Mediating Experimental Autoimmune Orchitis Induction in Mice1

“…TLR-initiated innate immune responses in innate immune cells facilitate antigen-specific adaptive immune responses by modulating lymphocyte proliferation and differentiation [19]. Notably, TLR2 and TLR4 are also expressed and functional in B cells [38]. The investigation on the potential role of TLRs in autonomously regulating B cell response in EAO would provide further insights into the mechanisms that TLR2 and TLR4 mediate EAO induction.…”

Loss of marginal zone B-cells in SHIVSF162P4 challenged rhesus macaques despite control of viremia to low or undetectable levels in chronic infection

“…Whether MZ B-cells can produce and secrete all of the cytokine/chemokines we detected by RNA needs further verification. While IL-10 secretion has been attributed to MZ B-cells, for example (Buchta and Bishop, 2014; Shen et al, 2013), RNA (cDNA) detection does not necessarily relate to translated protein as shown for IL-15 (Onu et al, 1997). The downregulation of complement component C3, but upregulation of MBL2 might indicate skewing of the complement system’s physiological roles beyond the scope of host defense as discussed by Kolev et al (Kolev et al, 2014).…”

“…Expression of TLRs on Rhesus macaque B-cells has not been described, but it might be similar to that of humans. TLRs are expressed to varying degrees on human B-cell subsets (Buchta and Bishop, 2014; Dorner et al, 2009). In mice, TLR3 seems to be somewhat more broadly expressed on MZ B-cells (Buchta and Bishop, 2014).…”

“…TLRs are expressed to varying degrees on human B-cell subsets (Buchta and Bishop, 2014; Dorner et al, 2009). In mice, TLR3 seems to be somewhat more broadly expressed on MZ B-cells (Buchta and Bishop, 2014). However, the contributions of TLR signaling to the development and function of human MZ B-cells have not been elucidated (Weill et al, 2009).…”

Regulation of humoral immunity by gut microbial products

“…B cells express TLR1, 2, 4, 6, 7, and 9, and activation of these TLRs increase B cell survival, antigen presentation, and antibody production. 16 In steady-states, the gut microbiota produce TLR ligands that activate B cells. For example, low levels of lipopolysaccharides from gram-negative bacteria activate B cells to induce CSR of the immunoglobulin (Ig) heavy chain gene to produce IgA.…”