Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

Ellen Marks; Carla Ortiz; Eirini Pantazi; Charlotte S Bailey; Graham M Lord; Thomas J Waldschmidt; Randolph J Noelle; Raul Elgueta

doi:10.3389/fimmu.2016.00643

Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

Ellen Marks, Carla Ortiz, Eirini Pantazi, Charlotte S Bailey, Graham M Lord, Thomas J Waldschmidt, Randolph J Noelle, Raul Elgueta

Diabetes

University of Iowa
Department of Mucosal Immunology, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.

Original language	English
Journal	Frontiers in Immunology
Volume	7
Issue number	643
Early online date	2016
DOIs	https://doi.org/10.3389/fimmu.2016.00643
Publication status	Published - 23 Dec 2016

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title = "Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response",

abstract = "Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.",

author = "Ellen Marks and Carla Ortiz and Eirini Pantazi and Bailey, {Charlotte S} and Lord, {Graham M} and Waldschmidt, {Thomas J} and Noelle, {Randolph J} and Raul Elgueta",

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AU - Marks, Ellen

AU - Ortiz, Carla

AU - Pantazi, Eirini

AU - Bailey, Charlotte S

AU - Lord, Graham M

AU - Waldschmidt, Thomas J

AU - Noelle, Randolph J

AU - Elgueta, Raul

PY - 2016/12/23

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N2 - Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.

AB - Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.

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DO - 10.3389/fimmu.2016.00643

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VL - 7

JO - Frontiers in Immunology

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Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

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