Abstract
Introduction: FcRL4 is an inhibitory receptor which is mainly expressed by B cells localised in the mucosa associated lymphoid tissue and at sites of chronic inflammation. FcRL4 can act as a low affinity IgA receptor, and FcRL4+ B cells from sites of inflammation carry captured IgA aggregates on their surface. FcRL4 expression, at a low level, can also be detected on peripheral blood (PB) CD21low/CD11c+ age related B cells (ABC).
We addressed the question whether the level of FcRL4 expression on ABC ex vivo or after stimulation allows them to capture IgA aggregates on their surface.
Methods: FcRL4 expression and IgA binding were analysed by flow cytometry in B cell populations from synovial fluid (SF), peripheral blood (PB), and tonsils, as well as TLR-7 and TLR-9β agonists and TGF-β stimulated PB B cells. PBMCs were treated with 0.1M glycine buffer (pH3) and human colostrum IgA to remove or add IgA to the B cell surface.
Results: The CD21loCD11chi phenotype and FcRL4 expression coincide in PBMC and SF B cells but only in a small proportion of tonsil B cells. While SF and tonsil FcRL4+ B cells carry IgA aggregates on their surface this was not detectable in PB B cells. In vitro stimulated CD21loCD11chi B cells significantly increased their FcRL4 expression and were able to capture IgA aggregates on their surface.
Conclusions: While circulating ABC express low but detectable levels of FcRL4, this is not sufficient to capture IgA aggregates. Upregulation of FcRL4 on CD21loCD11chi ABCs can allow them to capture IgAIC indicating that there is a threshold level of FcRL4 expression that is required to bind IgAIC and that additional stimulatory signals can enable IgA capture in ABC.
We addressed the question whether the level of FcRL4 expression on ABC ex vivo or after stimulation allows them to capture IgA aggregates on their surface.
Methods: FcRL4 expression and IgA binding were analysed by flow cytometry in B cell populations from synovial fluid (SF), peripheral blood (PB), and tonsils, as well as TLR-7 and TLR-9β agonists and TGF-β stimulated PB B cells. PBMCs were treated with 0.1M glycine buffer (pH3) and human colostrum IgA to remove or add IgA to the B cell surface.
Results: The CD21loCD11chi phenotype and FcRL4 expression coincide in PBMC and SF B cells but only in a small proportion of tonsil B cells. While SF and tonsil FcRL4+ B cells carry IgA aggregates on their surface this was not detectable in PB B cells. In vitro stimulated CD21loCD11chi B cells significantly increased their FcRL4 expression and were able to capture IgA aggregates on their surface.
Conclusions: While circulating ABC express low but detectable levels of FcRL4, this is not sufficient to capture IgA aggregates. Upregulation of FcRL4 on CD21loCD11chi ABCs can allow them to capture IgAIC indicating that there is a threshold level of FcRL4 expression that is required to bind IgAIC and that additional stimulatory signals can enable IgA capture in ABC.
| Original language | English |
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| Publication status | Published - 8 Dec 2022 |
| Event | British Society for Immunology Congress 2022 - Liverpool, United Kingdom Duration: 5 Dec 2022 → 8 Dec 2022 |
Conference
| Conference | British Society for Immunology Congress 2022 |
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| Abbreviated title | BSI Congress 2022 |
| Country/Territory | United Kingdom |
| City | Liverpool |
| Period | 5/12/22 → 8/12/22 |