Basis for the preferential expression of IgA by Peyer's patch B cells
Abstract
It is difficult to assess which heavy-chain (C$\sb{\rm H}$) genes are expressed by Peyer's patch (PP) germinal-center (GC) B-cells by assaying these cells either in vivo, or in in vitro cultures. Therefore, we examined the mRNAs they produce for various C$\sb{\rm H}$ transcripts by in situ hybridization. We found that approximately 50% of PP GC B-cells contain mRNA$\mu$, and of the remaining cells, 40% contain mRNA$\alpha$. Northern blot analysis showed that the messages correspond to sizes known to encode the membrane and secretory forms of IgM and IgA. None of the message was for C$\alpha$ germ-line transcripts. Finally, GC and sIgA$\sp+$ PP B-cells lack C$\sb{\rm H}$ genomic DNA 5$\sp\prime$ of C$\alpha$. Therefore, we believe most GC cells expressing mRNA$\alpha$ have undergone a DNA rearrangement as they switch to IgA expression. Our findings reflect the preference of PP GC B-cells to switch to IgA. The expression of IgA by PP GC B-cells in conventionally reared mice has been suggested to be due to either the chronic state of PP GCs or the GC microenvironment. To test these two alternative hypotheses, we attempted to raise GCs de novo in PPs of germ-free mice following oral administration of reovirus Type1/Lang, and in lymph-nodes (LNs) of conventionally reared mice after local parenteral infection. Transient GC responses occurred in each tissue following primary infection and secondary challenge. After reovirus infection, sIgA$\sp+$ B-cells were detected in PPs. In LNs, sIgG1$\sp+$ B-cells comprised the principle non-IgM$\sp+$/IgD$\sp+$ B-cell population. PP fragment cultures initiated following primary infection and secondary challenge produced reovirus-specific IgA, whereas LN cultures elaborated IgG1, but not IgA. Northern blot analysis detected C$\alpha$ germ-line transcripts in PPs, but not LNs; further substantiating a site-related bias in non-IgM$\sp+$/IgD$\sp+$ isotype expression. In conclusion, the transient nature of PP GCs in germ-free mice given reovirus orally suggests that a continual array of antigens may be required to maintain the chronic GCs found in conventionally reared mice. In addition, the preference for generating sIgA$\sp+$ B-cells in PPs appears to result from intrinsic features of the PP GC microenvironment, and not the persistence of the GC.
Subject Area
Cellular biology|Immunology|Biomedical research
Recommended Citation
Weinstein, Peter Douglas, "Basis for the preferential expression of IgA by Peyer's patch B cells" (1991). Dissertations available from ProQuest. AAI9125777.
https://repository.upenn.edu/dissertations/AAI9125777