The preference for switching to IgA expression by Peyer's patch germinal center B cells is likely due to the intrinsic influence of their microenvironment

Abstract

This study was aimed at determining whether the chronically activated physiologic state of Peyer's patch (PP) tissue is primarily responsible for the IgA isotype preference expressed by PP germinal centers (GC) and memory B cells. We have used reovirus type 1/Lang to stimulate acute, de novo GC reactions in lymph nodes (LN) or PP to test the possibility that the surface (s)IgA component of enteric responses is peculiar to the local gut microenvironment whether or not PP are in a state of chronic activation. GC were raised in PP of germ-free mice by oral administration of virus and in lymph nodes (LN) of conventionally reared mice by local parenteral infection. Transient GC reactions were found to develop with similar time courses in both PP and LN after both primary and secondary local infections with reovirus. sIgA+ B cells, which were the major non-sIgM+/sIgD+ population found to arise in GC of PP, were not found in the LN. In LN, sIgG1+ B cells comprised the predominant non-IgM/IgD bearing population that arise after local infection. Lymphoid fragment cultures of PP initiated in vitro as early as 5 days after in vivo infection contained detectable secreted reovirus-specific IgA, whereas IgG1 but no IgA was found in LN cultures. Northern blot analysis to detect C alpha and C gamma 1 germline transcripts further substantiated a site-related bias in the expression of non-IgM/IgD isotypes that was manifest within a few days after infection. In summation, these observations taken together suggest that the preference for generating sIgA+ B cells in PP may be the result of intrinsic features of their gut microenvironment.