The most IgA is produced at mucosal surfaces in response to antigenic exposure. While IgA is considered to be part of adaptive immune system, controversy still persists regarding signals needed for its production.
New article in journal Immunity may put an end to this discussion, finally. The authors, led by Albert Bendelac (he was one of the discoverer of NKT cells), have used IgA-seq methodology and showed that gut IgA production is mostly T-independent and mostly specific for gut microbiota.
Initially, the authors showed that proportion of gut microbiota both in small or large intestine are covered with IgA (there are IgA- and IgA+).
Next, the authors have used IgA-seq approach to phenotype microflora. This method consists of capturing of IgA from the feces followed by sequencing of antigens attached to IgA (in this case microbial 16S rRNA).
Interestingly, unlike IgA- microflora, there was a clear overlap between IgA+ microflora both from large and small intestine, implying common origin.
Next, the authors elucidated the origin of gut IgA. First, both wild-type and T cell-deficient mice found to produce comparable gut microbiota-centric IgA.
Second, no difference was found between wild-type and TFH-deficient mice (Bcl-6ΔT) either.
However, the authors showed that few selected microflora members, such as SFB and Mucispirillium could elicit T-dependent IgA response.
Finally, the authors' experiments revealed that most of gut IgA was produced by subset of non-canonical B1 cells called B1b cells in a T-independent manner.
In summary, this study showed that (1) most of small intestine microflora is coated with IgA (2) these IgA are produced in absence of T cell help (3) these IgA is derived from B1b cells whose repertoire was broad and of comparable diversity to that of canonical, spleen B cells and (4) some members of microflora, SFB and Mucispirillium did appear to induce IgA production via canonical T-dependent manner.
Why is this study relevant? First, it suggests that gut immune health is established in absence of T helper cells via B1b cells. Not much is known about B1b population. Is it possible that many gut immune pathologies (ulcerative colitis, celiac disease, crohn's disease) originate because of alteration in B1b cells?
David Usharauli
Next, the authors have used IgA-seq approach to phenotype microflora. This method consists of capturing of IgA from the feces followed by sequencing of antigens attached to IgA (in this case microbial 16S rRNA).
Interestingly, unlike IgA- microflora, there was a clear overlap between IgA+ microflora both from large and small intestine, implying common origin.
Next, the authors elucidated the origin of gut IgA. First, both wild-type and T cell-deficient mice found to produce comparable gut microbiota-centric IgA.
However, the authors showed that few selected microflora members, such as SFB and Mucispirillium could elicit T-dependent IgA response.
Finally, the authors' experiments revealed that most of gut IgA was produced by subset of non-canonical B1 cells called B1b cells in a T-independent manner.
In summary, this study showed that (1) most of small intestine microflora is coated with IgA (2) these IgA are produced in absence of T cell help (3) these IgA is derived from B1b cells whose repertoire was broad and of comparable diversity to that of canonical, spleen B cells and (4) some members of microflora, SFB and Mucispirillium did appear to induce IgA production via canonical T-dependent manner.
Why is this study relevant? First, it suggests that gut immune health is established in absence of T helper cells via B1b cells. Not much is known about B1b population. Is it possible that many gut immune pathologies (ulcerative colitis, celiac disease, crohn's disease) originate because of alteration in B1b cells?
David Usharauli
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