Macrophage polarization to a unique phenotype driven by B cells.
Regulation of adaptive immunity by innate immune cells is widely accepted. Conversely, adaptive immune cells can also regulate cells of the innate immune system. Here, we report for the first time the essential role of B cells in regulating macrophage (Mφ) phenotype. In vitro B cell/Mφ co-culture experiments together with experiments in transgenic mice models for B-cell deficiency or overexpression showed B1 cells to polarize Mφ to a distinct phenotype. This was characterized by downregulated TNF-α, IL-1β and CCL3, but upregulated IL-10 upon LPS stimulation; constitutive expression of M2 Mφ markers (e.g. Ym1, Fizz1) and overexpression of TRIF-dependent cytokines (IFN-β, CCL5). Mechanistically, this phenotype was linked to a defective NF-κB activation, but a functional TRIF/STAT1 pathway. B1-cell-derived IL-10 was found to be instrumental in the polarization of these Mφ. Finally, in vivo relevance of B1-cell-induced Mφ polarization was confirmed using the B16 melanoma tumor model where adoptive transfer of B1 cells induced an M2 polarization of tumor-associated Mφ. Collectively, our results define a new mechanism of Mφ polarization wherein B1 cells play a key role in driving Mφ to a unique, but M2-biased phenotype. Future studies along these lines may lead to targeting of B1 cells to regulate Mφ response in inflammation and cancer.
Wong
Siew-Cheng
SC
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.
Puaux
Anne-Laure
AL
Chittezhath
Manesh
M
Shalova
Irina
I
Kajiji
Tasneem S
TS
Wang
Xiaojie
X
Abastado
Jean-Pierre
JP
Lam
Kong-Peng
KP
Biswas
Subhra K
SK
D056704:Adaptive Immunity; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D019264:Adoptive Transfer; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008546:Melanoma, Experimental; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D015533:Transcriptional Activation
D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D016207:Cytokines; D016328:NF-kappa B; C476286:Ticam1 protein, mouse