| First Author | Lin Q | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 11 | Pages | 3199-3210 |
| PubMed ID | 30373853 | Mgi Jnum | J:267721 |
| Mgi Id | MGI:6258091 | Doi | 10.4049/jimmunol.1701487 |
| Citation | Lin Q, et al. (2018) FcgammaRIIb on B Cells and Myeloid Cells Modulates B Cell Activation and Autoantibody Responses via Different but Synergistic Pathways in Lupus-Prone Yaa Mice. J Immunol 201(11):3199-3210 |
| abstractText | C57BL/6 (B6).FcgammaRIIb(-/-) Yaa mice spontaneously develop lethal lupus nephritis. To define the cell type-specific role of FcgammaRIIb in Yaa-associated lupus, we established B cell- (CD19(Cre) Yaa), myeloid cell- (C/EBPalpha(Cre) Yaa), and dendritic cell- (DC) (CD11c(Cre) Yaa) specific FcgammaRIIb-deficient B6.Yaa mouse strains. CD19(Cre) Yaa mice developed milder lupus than B6.FcgammaRIIb(-/-) Yaa mice, indicating that FcgammaRIIb deficiency on B cells is not sufficient for the development of severe disease. Surprisingly, C/EBPalpha(Cre) Yaa mice also showed autoantibody production and mild lupus similar to that in CD19(Cre) Yaa mice, whereas CD11c(Cre) Yaa mice stayed disease free. These observations indicate that FcgammaRIIb deficiency in B cells and myeloid cells, but not DCs, contributes to the severe disease in B6.FcgammaRIIb(-/-) Yaa mice. Flow cytometric analysis showed that the frequency of peripheral Gr-1(-) but not Gr-1(+) monocyte was increased in B6.FcgammaRIIb(-/-) Yaa and C/EBPalpha(Cre) Yaa but not CD19(Cre) Yaa mice, suggesting a link between FcgammaRIIb deficiency on myeloid cells and the high frequency of Gr-1(-) monocytes. RNA sequencing revealed that compared with Gr-1(+) monocytes, Gr-1(-) monocytes expressed higher levels of the B cell-stimulating cytokines BSF-3, IL-10, and IL-1beta, the DC markers CD11c, CD83, and Adamdec1, and the antiapoptotic factors Bcl2 and Bcl6. In conclusion, in Yaa-associated lupus nephritis, FcgammaRIIb on B cells and myeloid cells modulates B cell activation via different but synergistic pathways. Gr-1(-) monocytes are the most likely candidate myeloid cells involved. |
