Abstract
The germinal center (GC) reaction in Peyer′s patches (PP) requires continuous access to antigens, but how this is achieved is not known. Here we show that activated antigen-specific CCR6+CCR1+GL7− B cells make close contact with M cells in the subepithelial dome (SED). Using in situ photoactivation analysis of antigen-specific SED B cells, we find migration of cells towards the GC. Following antigen injection into ligated intestinal loops containing PPs, 40% of antigen-specific SED B cells bind antigen within 2 h, whereas unspecifc cells do not, indicating B cell-receptor involvment. Antigen-loading is not observed in M cell-deficient mice, but is unperturbed in mice depleted of classical dendritic cells (DC). Thus, we report a M cell-B cell antigen-specific transporting pathway in PP that is independent of DC. We propose that this antigen transporting pathway has a critical role in gut IgA responses, and should be taken into account when developing mucosal vaccines.
Highlights
The germinal center (GC) reaction in Peyer′s patches (PP) requires continuous access to antigens, but how this is achieved is not known
We have developed an adoptive transfer model based on NP-specific B1–8hi IgH knock-in λ-expressing GFP+ splenic B cells and NPhapten conjugated to cholera toxin (NP-CT) as an oral immunogen to study gut IgA responses[16,32,41] (Fig. 1a, b)
Following an oral immunization with NP-CT we found that a majority of NP-specific GFP+ B cells in the PPs were found in the GC compartment (Fig. 1c)
Summary
The germinal center (GC) reaction in Peyer′s patches (PP) requires continuous access to antigens, but how this is achieved is not known. Adjacent to the M cells is the SED region that hosts multiple cell types, including different subsets of dendritic cells (DCs), macrophages, neutrophils, B and T cells[3,15,16]. When activated B cells start to express CCR6 they can move into the SED, where they interact with other cells, in particular, CD11b+ CD8− DCs23,24 These DCs express integrin αvβ[8] that can activate latent transforming growth factor β (TGFβ), the prime switch factor required for IgA CSR25–29. IgA CSR in SED depends on pre-GC B cell interactions with the DCs. it is believed that the IgA-switched B cells can return to the follicle by directed migration and participate in the GC response[2]. We have identified that in CD40-deficient mice substantial IgA
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