. 2023 Oct 5;14:1233085. doi: 10.3389/fimmu.2023.1233085

Table 2.

Breg cell phenotypes discovered in mouse cancer models.

Breg type	Phenotype	Cancer	Location	Expressed molecules	Description
B10 Breg	CD19⁺CD21^hi	Papilloma	Tumor tissues	IL-10	Promote TNF-α mediated squamous carcinogenesis (66).
B10 Breg	CD19⁺CD5⁺CD1d^hi	Non-hodgkin lymphoma	Tumor tissues, spleen	IL-10	Inhibit lymphoma depletion and monocyte activation induced by CD20 mAbs (67).
IL-35⁺ Breg	CD19⁺ CD5⁺CD1d^hi	PanIN	Tumor tissues	IL-10, IL-35	BTK signaling pathway regulated; promote tumor progression (68).
	CD19⁺ CD5⁺CD1d^hi	Pancreatic cancer	Tumor tissues	IL-35	Promote tumor progression via IL-35 (69).
	CD19⁺ CD21^hiCD5⁺CD1d^hi	Pancreatic cancer	Tumor tissues	IL-10, IL-35	Cause CD8⁺ T cell exclusion, tumor progression, and immunotherapy resistance via the IL35/gp130/STAT3 pathway (53, 60, 70).
PD-L1⁺ Breg	CD19⁺PD-1^-PD-L1⁺	4T1 breast cancer	Spleen, PBMCs	—	MDSC-induced; inhibit proliferation and production of IFN-γ by T cells (71)
IgA⁺ Breg	CD19⁺IgA⁺PD-L1⁺	Colorectal tumor	Tumor tissues	IL-10, TGF-β, IgA	Inhibit CD8⁺ T cell proliferation and activation (72)
	CD19⁺CD20^lowB220^lowIgA⁺PD-L1⁺	Prostate cancer	Tumor tissues	IL-10, IgA	Induce CD8⁺ T cell exhaustion, suppress cytotoxic CD8⁺ T cell activation through PD-L1 and IL-10 (65).
	CD19⁺B220^lowCD138⁺IgA⁺PD-L1⁺	Hepatocellular carcinoma	Tumor tissue	IL-10, IgA,	Suppress cytotoxic CD8⁺ T cell, cause tumor progression (73).
T2-MZP Breg	B220⁺CD23⁺IgM^hiCD21^hi	Melanoma	Tumor-draining LNs	IgM	Enriched in tumor-draining LNs; promote tumor progression (74).
——	CD19⁺CD81^hiCD25⁺	4T1 breast cancer, B16F10 melanoma	Tumor tissues	TGF-β	Induce Treg cell proliferation and inhibit CD8⁺ T cell function (75).
——	CD86^hiIAd^hiCD62L^hiLAP⁺CD44^lowPD-L1^hi	EMT-6 breast cancer	Tumor tissues	TGF-β	Suppress T cell, Th1 cell, and NK cell proliferation; promote tumor progression (76).
——	Stat3⁺, CD19⁺CD25^hiB7-H1^hiCD81^hiCCR6^hiCD86^hiCD62L^lowIgM^dim	4T1 breast cancer	Tumor tissues	TGF-β	TGF-β mediated transformation of resting CD4⁺ T cells into FoxP3+ Treg cells; lead to tumor metastasis (77).
——	CD20^lowCD137^lo	4T1 breast cancer	Tumor tissues		Cause tumor progression and metastasis (78).
——	CD20⁺	Prostate cancer	Tumor tissues	Lymphotoxin	Lymphotoxin-producing Breg cells can be recruited by CXCL13, which stimulate the lymphotoxin receptor on cancer cells, induce IKKα nuclear translocation and STAT3 activation, and promote cancer metastasis (79, 80).

LN, lymph node; PanIN, pancreatic intraepithelial neoplasia; PBMC, peripheral blood mononuclear cells; LN, lymph node; B10 Breg, IL-10 producing regulatory B cell; T2-MZP, transitional 2-marginal zone precursor; MDSC, myeloid-derived suppressor cell; NK cell, natural killer cell; BKT, Bruton’s tyrosine kinase; CXCL13, CXC-chemokine ligand 13; IKK, inflammation-responsive IκB kinase; hi, high; dim, medium.