Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


FcgammaRIIb on B Cells and Myeloid Cells Modulates B Cell Activation and Autoantibody Responses via Different but Synergistic Pathways in Lupus-Prone Yaa Mice.


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- (CD19Cre Yaa), myeloid cell- (C/EBPalphaCre Yaa), and dendritic cell- (DC) (CD11cCre Yaa) specific FcgammaRIIb-deficient B6.Yaa mouse strains. CD19Cre 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/EBPalphaCre Yaa mice also showed autoantibody production and mild lupus similar to that in CD19Cre Yaa mice, whereas CD11cCre 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/EBPalphaCre Yaa but not CD19Cre 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.

Authors: Lin Q, Ohtsuji M, Amano H, Tsurui H, Tada N, Sato R, Fukuyama H, Nishimura H, Verbeek JS, Hirose S
Journal: J Immunol. 2018 Dec 1;201(11):3199-3210. doi: 10.4049/jimmunol.1701487. Epub 2018
Year: 2018
PubMed: PMID: 30373853 (Go to PubMed)