Differences of CD19<sup>+</sup>IL-10<sup>+</sup> B cell and its subsets contents in peripheral blood and cancer tissues of patients with colorectal cancer and its clinical significances_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Jie , CHEN Xiaolong , HU Xinyu , ZUO Zonglin , CHEN Peng , FENG Libo , ZOU Qingwei ,  XIA Dong

Department of Gastrointestinal Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;

Corresponding author：

XIA Dong, Email: juliahhy@aliyun.com

Keywords：

colorectal cancer; CD19⁺ IL-10⁺ B cell; regulatory B cell

DOI：

10.7507/1007-9424.201903070

Video：

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Objectives To investigate contents and clinical significances of CD19⁺IL-10⁺ B cell and its subsets in peripheral blood monouclear cell (PBMC) and cancer tissue of patient with colorectal cancer (CRC). Methods Thirty-eight patients with CRC underwent surgery from November 2017 to November 2018 in this hospital were enrolled as a trail group. The proportions of CD19⁺IL-10⁺ B cell, CD19⁺IL-10⁺CD24^hiCD38^hi B cell, CD19⁺IL-10⁺CD24^intCD38^int B cell, and CD19⁺IL-10⁺CD24^hiCD38^– B cell in the CD19⁺ B cells in the PBMC, cancer tissue and paracancer tissue of these patients were detected by the flow cytometry. Thirty-seven healthy volunteers were selected as a control group and the same cell types same as the trail group were detected by the same method in the PBMC only. Results ① The contents of CD19⁺IL-10⁺ B cell and CD19⁺IL-10⁺CD24^hiCD38^hi B cell of the PBMC in the trail group were significantly higher than those in the control group (t=9.09, P<0.01; t=9.36, P<0.01, respectively), which of the cancer tissues in the trail group were significantly higher than those in the corresponding paracancer tissues (t=11.67, P<0.01; t=19.64, P<0.01, respectively), while the content of CD19⁺IL-10⁺CD24^hiCD38^– B cell of the PBMC in the trail group was significantly lower than that in the control group (t=6.15, P<0.01). But the CD19⁺IL-10⁺CD24^intCD38^int B cell had no significant difference of the PBMC between these two groups (t=1.78, P=0.08). ② The contents of CD19⁺IL-10⁺ B cell and CD19⁺IL-10⁺CD24^hiCD38^hi B cell of the PBMC in the CRC patients with stage Ⅲ+Ⅳ were significantly higher than those in the CRC patients with stage Ⅰ+Ⅱ (t=5.39, P<0.01; t=3.13, P<0.01, respectively). The others all had no significant differences (P>0.05). Conclusion CD19⁺IL-10⁺ B cells are significantly increased in PBMC and cancer tissue of patient with CRC and with advanced CRC (TNM stage Ⅲ+Ⅳ), further more, main increasing subgroup of CD19⁺IL-10⁺ B cell is CD19⁺IL-10⁺CD24^hiCD38^hi B cell, which indicates that CD19⁺IL-10⁺ B cell and CD19⁺IL-10⁺CD24^hiCD38^hi B cell might participate in tumorigenesis and tumor progress of CRC.

Citation： XU Jie, CHEN Xiaolong, HU Xinyu, ZUO Zonglin, CHEN Peng, FENG Libo, ZOU Qingwei, XIA Dong. Differences of CD19⁺IL-10⁺ B cell and its subsets contents in peripheral blood and cancer tissues of patients with colorectal cancer and its clinical significances. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(7): 808-813. doi: 10.7507/1007-9424.201903070 Copy

1.	Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol, 1995, 155(3): 1151-1164.
2.	Feuerer M, Hill JA, Mathis D, et al. Foxp3⁺ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol, 2009, 10(7): 689-695.
3.	Saito T, Nishikawa H, Wada H, et al. Two FOXP3⁺CD4⁺ T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med, 2016, 22(6): 679-684.
4.	de Andrés C, Tejera-Alhambra M, Alonso B, et al. New regulatory CD19⁺CD25⁺ B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids. J Neuroimmunol, 2014, 270(1-2): 37-44.
5.	Michel L, Chesneau M, Manceau P, et al. Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis. Clin Immunol, 2014, 155(2): 198-208.
6.	Oka A, Ishihara S, Mishima Y, et al. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn’s disease. Inflamm Bowel Dis, 2014, 20(2): 315-328.
7.	Menon M, Blair PA, Isenberg DA, et al. A regulatory feedback between plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity, 2016, 44(3): 683-697.
8.	Cui D, Zhang L, Chen J, et al. Changes in regulatory B cells and their relationship with rheumatoid arthritis disease activity. Clin Exp Med, 2015, 15(3): 285-292.
9.	Kristensen B, Hegedüs L, Lundy SK, et al. Characterization of regulatory B cells in Graves’ disease and Hashimoto’s thyroiditis. PLoS One, 2015, 10(5): e0127949.
10.	Mutnal MB, Hu S, Schachtele SJ, et al. Infiltrating regulatory B cells control neuroinflammation following viral brain infection. J Immunol, 2014, 193(12): 6070-6080.
11.	Liu Y, Cheng LS, Wu SD, et al. IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection. Clin Sci (Lond), 2016, 130(11): 907-919.
12.	Ringelstein-Harlev S, Avivi I, Fanadka M, et al. Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation. Cancer Immunol Immunother, 2018, 67(5): 739-748.
13.	Gudbrandsdottir S, Brimnes M, Køllgaard T, et al. Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia. Eur J Haematol, 2018, 100(1): 45-52.
14.	Chu Z, Zou W, Xu Y, et al. The regulatory roles of B cell subsets in transplantation. Expert Rev Clin Immunol, 2018, 14(2): 115-125.
15.	Baran T, Boratyńska M. Immunoregulatory role of B lymphocytes in alloresponse to kidney transplant. Postepy Hig Med Dosw (Online), 2017, 71(0): 254-266.
16.	Zhang Y, Gallastegui N, Rosenblatt JD. Regulatory B cells in anti-tumor immunity. Int Immunol, 2015, 27(10): 521-530.
17.	Schwartz M, Zhang Y, Rosenblatt JD. B cell regulation of the anti-tumor response and role in carcinogenesis. J Immunother Cancer, 2016, 4: 40.
18.	Qian L, Bian GR, Zhou Y, et al. Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer. Cent Eur J Immunol, 2015, 40(2): 263-265.
19.	Wang WW, Yuan XL, Chen H, et al. CD19⁺CD24^hiCD38^hi Bregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer. Oncotarget, 2015, 6(32): 33486-33499.
20.	Xiao X, Lao XM, Chen MM, et al. PD-1^hi identifies a novel regulatory B-cell population in human hepatoma that promotes disease progression. Cancer Discov, 2016, 6(5): 546-559.
21.	Zhou X, Su YX, Lao XM, et al. CD19⁺IL-10⁺ regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4⁺ T cells to CD4⁺Foxp3⁺ regulatory T cells. Oral Oncol, 2016, 53: 27-35.
22.	Carsetti R, Rosado MM, Wardmann H. Peripheral development of B cells in mouse and man. Immunol Rev, 2004, 197: 179-191.
23.	Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev, 2011, 241(1): 260-268.
24.	Cai X, Zhang L, Wei W. Regulatory B cells in inflammatory diseases and tumor. Int Immunopharmacol, 2019, 67: 281-286.
25.	Sarvaria A, Madrigal JA, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol, 2017, 14(8): 662-674.
26.	Blair PA, Noreña LY, Flores-Borja F, et al. CD19⁺CD24^hiCD38^hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity, 2010, 32(1): 129-140.
27.	Shimabukuro-Vornhagen A, Schlößer HA, Gryschok L, et al. Characterization of tumor-associated B-cell subsets in patients with colorectal cancer. Oncotarget, 2014, 5(13): 4651-4664.
28.	Gheybi MK, Farrokhi S, Ravanbod MR, et al. The correlation of CD19⁺CD24⁺CD38⁺ B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patients. Breast Cancer, 2017, 24(6): 756-764.

1. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol, 1995, 155(3): 1151-1164.
2. Feuerer M, Hill JA, Mathis D, et al. Foxp3⁺ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol, 2009, 10(7): 689-695.
3. Saito T, Nishikawa H, Wada H, et al. Two FOXP3⁺CD4⁺ T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med, 2016, 22(6): 679-684.
4. de Andrés C, Tejera-Alhambra M, Alonso B, et al. New regulatory CD19⁺CD25⁺ B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids. J Neuroimmunol, 2014, 270(1-2): 37-44.
5. Michel L, Chesneau M, Manceau P, et al. Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis. Clin Immunol, 2014, 155(2): 198-208.
6. Oka A, Ishihara S, Mishima Y, et al. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn’s disease. Inflamm Bowel Dis, 2014, 20(2): 315-328.
7. Menon M, Blair PA, Isenberg DA, et al. A regulatory feedback between plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity, 2016, 44(3): 683-697.
8. Cui D, Zhang L, Chen J, et al. Changes in regulatory B cells and their relationship with rheumatoid arthritis disease activity. Clin Exp Med, 2015, 15(3): 285-292.
9. Kristensen B, Hegedüs L, Lundy SK, et al. Characterization of regulatory B cells in Graves’ disease and Hashimoto’s thyroiditis. PLoS One, 2015, 10(5): e0127949.
10. Mutnal MB, Hu S, Schachtele SJ, et al. Infiltrating regulatory B cells control neuroinflammation following viral brain infection. J Immunol, 2014, 193(12): 6070-6080.
11. Liu Y, Cheng LS, Wu SD, et al. IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection. Clin Sci (Lond), 2016, 130(11): 907-919.
12. Ringelstein-Harlev S, Avivi I, Fanadka M, et al. Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation. Cancer Immunol Immunother, 2018, 67(5): 739-748.
13. Gudbrandsdottir S, Brimnes M, Køllgaard T, et al. Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia. Eur J Haematol, 2018, 100(1): 45-52.
14. Chu Z, Zou W, Xu Y, et al. The regulatory roles of B cell subsets in transplantation. Expert Rev Clin Immunol, 2018, 14(2): 115-125.
15. Baran T, Boratyńska M. Immunoregulatory role of B lymphocytes in alloresponse to kidney transplant. Postepy Hig Med Dosw (Online), 2017, 71(0): 254-266.
16. Zhang Y, Gallastegui N, Rosenblatt JD. Regulatory B cells in anti-tumor immunity. Int Immunol, 2015, 27(10): 521-530.
17. Schwartz M, Zhang Y, Rosenblatt JD. B cell regulation of the anti-tumor response and role in carcinogenesis. J Immunother Cancer, 2016, 4: 40.
18. Qian L, Bian GR, Zhou Y, et al. Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer. Cent Eur J Immunol, 2015, 40(2): 263-265.
19. Wang WW, Yuan XL, Chen H, et al. CD19⁺CD24^hiCD38^hi Bregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer. Oncotarget, 2015, 6(32): 33486-33499.
20. Xiao X, Lao XM, Chen MM, et al. PD-1^hi identifies a novel regulatory B-cell population in human hepatoma that promotes disease progression. Cancer Discov, 2016, 6(5): 546-559.
21. Zhou X, Su YX, Lao XM, et al. CD19⁺IL-10⁺ regulatory B cells affect survival of tongue squamous cell carcinoma patients and induce resting CD4⁺ T cells to CD4⁺Foxp3⁺ regulatory T cells. Oral Oncol, 2016, 53: 27-35.
22. Carsetti R, Rosado MM, Wardmann H. Peripheral development of B cells in mouse and man. Immunol Rev, 2004, 197: 179-191.
23. Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev, 2011, 241(1): 260-268.
24. Cai X, Zhang L, Wei W. Regulatory B cells in inflammatory diseases and tumor. Int Immunopharmacol, 2019, 67: 281-286.
25. Sarvaria A, Madrigal JA, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol, 2017, 14(8): 662-674.
26. Blair PA, Noreña LY, Flores-Borja F, et al. CD19⁺CD24^hiCD38^hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity, 2010, 32(1): 129-140.
27. Shimabukuro-Vornhagen A, Schlößer HA, Gryschok L, et al. Characterization of tumor-associated B-cell subsets in patients with colorectal cancer. Oncotarget, 2014, 5(13): 4651-4664.
28. Gheybi MK, Farrokhi S, Ravanbod MR, et al. The correlation of CD19⁺CD24⁺CD38⁺ B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patients. Breast Cancer, 2017, 24(6): 756-764.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Differences of CD19⁺IL-10⁺ B cell and its subsets contents in peripheral blood and cancer tissues of patients with colorectal cancer and its clinical significances

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Differences of CD19+IL-10+ B cell and its subsets contents in peripheral blood and cancer tissues of patients with colorectal cancer and its clinical significances

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Differences of CD19⁺IL-10⁺ B cell and its subsets contents in peripheral blood and cancer tissues of patients with colorectal cancer and its clinical significances