Macrophage- and dendritic cell—dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF

TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways

“…It is generally accepted that activated Th cells produce these cytokines which in turn directly modulate B cells. Nonetheless, there is accumulating evidence that macrophages affect B cell proliferation and differentiation (Craxton et al, 2003;Fagarasan and Honjo, 2000;Litinskiy et al, 2002). We have shown that APRIL, as well as BAFF, are produced by TGFβ1-stimulated mouse macrophages (Kim et al, 2008).…”

TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts

“…An obvious candidate is the membrane-bound form of BAFF that has been identified on myeloid cells. 7,8 Thus, productive signaling through TACI may require cell-cell contacts, ensuring that the signal is delivered at specific sites, and not in a systemic manner. BAFF-R, in contrast, may also respond to soluble BAFF 3-mer, which represent the majority of systemic BAFF.…”

“…[4][5][6] BAFF is either expressed at the cell surface or released into a soluble form through cleavage by an uncharacterized furin. [7][8][9] Members of the TNF family usually assemble as trimers, 10 but soluble BAFF was crystallized both as a trimer and as a virus-like structure resulting from the ordered assembly of 20 trimers through an unusually long loop of BAFF between ␤-sheets D and E (DE loop). 11,12 Although the physiologic relevance of BAFF 60-mer has not been studied, recent work showed that BAFF 60-mer was also produced by cells expressing BAFF endogenously and that the 60-mer was moderately more potent than the 3-mer at costimulating BCR-induced thymidine uptake in primary B cells.…”

BAFF and LPS cooperate to induce B cells to become susceptible to CD95/Fas‐mediated cell death

“…For instance, engagement of TLR4 by LPS stimulates myeloid DC and macrophages to secrete BAFF, which promotes BCR-and CD40-induced B cell proliferation [10] and favors immunoglobulin class switch recombination [11]. DC can also be triggered to produce BAFF by the TLR2 ligand peptidoglycan [12] and by nucleic acid-containing immune complexes, presumably via TLR9 [13]. These findings suggest that BAFF may be produced by DC and other cells in response to pathogens to promote rapid production of protective Ab.…”

“…Consistent with this model, we and others have found that mouse and human DC promote B cell proliferation in vitro by secreting BAFF. However, B cells must be triggered via their B cell receptors (BCR) to be most responsive to BAFF [12,15].…”