Abstract
Chemokine receptor CXCR5-mediated control of B cell trafficking in the lymphoid tissues plays a central role in orchestrating the B cell function, which not only guides the colocalization of B cells with follicular helper T cells in the follicular mantle zone but also determines the position of germinal center dark and light zones. However, the mechanisms that regulate the expression of CXCR5 in B cells remain unclear. Here, we show that the expression level of CXCR5 in B cells was substantially reduced in vitro culture conditions, while being maintained in the presence of CD40 signals. Furthermore, CD40 signaling promotes CXCR5 expression in B cells at least partially through noncanonical NF-κB signaling pathway activation. However, other non-B cells also contributed to the optimal expression of CXCR5 in B cells through cell-cell contact and cytokine secretion. Our findings suggest that CD40 signaling-mediated activation of the noncanonical NF-κB pathway promotes the expression of CXCR5 in a B cell-intrinsic way to orchestrate the trafficking of B cells.
Highlights
B cells are key players of the adaptive humoral immune, with roles including supporting follicular helper T-cell generation and producing antibodies [1, 2]
CXCR5-mediated control of B cell trafficking plays a cardinal role in orchestrating the B cell functions, little is known about the underlying mechanisms that regulate the expression of CXCR5 in B cells
The levels of CXCR5 in B cells were detected with flow cytometer by staining CD19 and CXCR5 (Figure 1(a)) and displayed a dramatic reduction in a time-dependent manner, while freshly isolated B cells displayed constitutive CXCR5 expression, reflected by mean fluorescence intensity (MFI) of CXCR5 (Figures 1(b) and 1(c)) and frequencies of CXCR5+ cells (Figure 1(d)) in B cells, suggesting that the microenvironmental cues in vivo were necessary for maintaining CXCR5 expression in B cells
Summary
B cells are key players of the adaptive humoral immune, with roles including supporting follicular helper T-cell generation and producing antibodies [1, 2]. The outcome of these functions relies on the finely tuned traffic of B cells [3]. CXC chemokine receptor 5-mediated signals play a central role in orchestrating B cell trafficking in the lymphoid tissues, such as spleen and lymph nodes [4]. CXCR5-mediated control of B cell trafficking plays a cardinal role in orchestrating the B cell functions, little is known about the underlying mechanisms that regulate the expression of CXCR5 in B cells
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