Chloroquine Suppresses Effector B-Cell Functions and Has Differential Impact on Regulatory B-Cell Subsets

• Published in: Frontiers in immunology Vol. 13; p. 818704
• Main Authors: Ma, Xin, Dai, Yang, Witzke, Oliver, Xu, Shilei, Lindemann, Monika, Kribben, Andreas, Dolff, Sebastian, Wilde, Benjamin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.02.2022
• Subjects: Adult; Aged; B-cells; B-Lymphocytes, Regulatory - drug effects; B-Lymphocytes, Regulatory - metabolism; Cell Proliferation - drug effects; chloroquine; Chloroquine - pharmacology; effector B-cells; Female; Granzymes - metabolism; Humans; Immunology; Interleukin-10 - metabolism; Kidney Transplantation; Leukocytes, Mononuclear - cytology; Lymphocyte Activation - drug effects; Male; Middle Aged; regulatory B (Breg) cells; renal transplantation; Toll-Like Receptor 9 - metabolism; chloroquine; regulatory B (Breg) cells; B-cells; effector B-cells; renal transplantation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.818704

Chloroquine (CQ) is approved for treatment of B-cell mediated diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the exact mode of action in these diseases has not been studied and it remains unclear which effect CQ has on B-cells. Thus, it was the aim of this study to investigate to which extent CQ affects functionality of effector and regulatory B-cell. For this purpose, B-cells were isolated from peripheral blood of healthy controls and renal transplant patients. B-cells were stimulated in presence or absence of CQ and Interleukin-10 (IL-10) and Granzyme B (GrB) secretion were assessed. In addition, effector functions such as plasma cell formation, and Immunoglobulin G (IgG) secretion were studied. CQ suppressed Toll-Like-Receptor (TLR)-9 induced B-cell proliferation in a dose-dependent manner. IL-10 regulatory B-cells were suppressed by CQ already at low concentrations whereas anti-IgG/IgM-induced GrB secreting regulatory B-cells were less susceptible. Plasma blast formation and IgG secretion was potently suppressed by CQ. Moreover, purified B-cells from renal transplant patients were also susceptible to CQ-induced suppression of effector B-cell functions as observed by diminished IgG secretion. In conclusion, CQ had a suppressive effect on IL-10 regulatory B-cells whereas GrB secreting regulatory B-cells were less affected. Effector functions of B-cells such as plasma blast formation and IgG secretion were also inhibited by CQ. Effector B-cells derived from renal transplant patients already under immunosuppression could be suppressed by CQ. These findings may partly explain the clinical efficacy of CQ in B-cell mediated autoimmune diseases. The application of CQ in other disease contexts where suppression of effector B-cells could offer a benefit, such as renal transplantation, may hypothetically be advantageous.