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

Ellen Marks, King's College London
Carla Ortiz, King's College London
Eirini Pantazi, King's College London
Charlotte S. Bailey, King's College London



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 a for RA (dnRAR alpha) 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 S1P(1) in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RAR alpha 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.