Biological Features of CD5+ CD19+ B1 Cell and Natural IgM (VH4-34) in Chronic Lymphocytic Leukemia vs. Multiple Sclerosis
-
Shaghayegh Pezeshki
,
Mir Hadi Jazayeri
,
Bahram Chahardouli
,
Nader Tajik
,
Seyyed Massood Nabavi
,
Mahdi Akbarzadeh
Abstract
Chronic lymphocytic leukemia (CLL) is the clonal expansion of mature CD5+ B cells and the most common lymphoproliferative disease in adults (B1-CLL). B1 cells' anti-inflammatory effects include the production of natural IgM (nIgM) by the spleen and bone marrow, decreased inflammatory cytokines as a primary response to maintaining tissue homeostasis, and enhanced release of transforming growth factor β (TGFβ).
We used the flow cytometry technique in peripheral blood from patients with CLL and multiple sclerosis (MS) to immunophenotype B cells and their subpopulations. Whole blood from CLL and MS patients, as well as healthy controls, was used to detect nIgM using the VH4-34 gene copy number and real-time RT-PCR.
We found that the proportion of CD5+ B cells was significantly lower in MS patients than in the control group and that CD5+ B lymphocytes were significantly higher in CLL patients than in the control group. Compared to the control group, CLL patients had significantly higher levels of the VH4-34 gene copy number. On the contrary, MS patients had significantly lower VH4-34 gene copy number levels compared to the control group.
As the number of antibodies in CLL patients increases due to the high number of B1 cells, we propose a new way to treat MS by extracting this natural antibody from the sera of CLL patients and injecting it into MS patients.
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22. Magatti M, Masserdotti A, Cargnoni A, Papait A, Stefani FR, Silini AR, et al. The role of b cells in pe pathophysiology: A potential target for perinatal cell-based therapy? Int J Mol Sci. 2021;22(7).
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24. Calvo J, Places L, Espinosa G, Padilla O, Vilà JM, Villamor N, et al. Identification of a natural soluble form of human CD5. Tissue Antigens. 1999;54(2):128–37.
25. Rovituso DM, Duffy CE, Schroeter M, Kaiser CC, Kleinschnitz C, Bayas A, et al. The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients. Sci Rep. 2015;5(9):1–8.
26. Tørring C, Petersen CC, Bjerg L, Kofod-Olsen E, Petersen T, Höllsberg P. The B1-cell subpopulation is diminished in patients with relapsing-remitting multiple sclerosis. J Neuroimmunol. 2013;262(1–2):92–9.
27. Aziz M, Holodick NE, Rothstein TL, Wang P. The role of B-1 cells in inflammation. Immunol Res. 2015;63(1–3):153–66.
28. Zhang X. Regulatory functions of innate-like B cells. Cell Mol Immunol. 2013;10(2):113–21.
29. Vyshkina T, Kalman B. Autoantibodies and neurodegeneration in multiple sclerosis. Lab Investig. 2008;88(8):796–807.
30. Fetter T, Niebel D, Braegelmann C, Wenzel J. Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases-Implications for Therapeutic Approaches. Cells. 2020;9(12).
31. Roudafshani Z, Jazayeri MH, Mahmoudi AR, Nedaeinia R, Safari E, Jazayeri A. Evaluation of the frequency of CD5+ B cells as natural immunoglobulin M producers and circulating soluble CD5 in patients with bladder cancer. Mol Biol Rep. 2019;46(6):6405–11.
32. Justyna W. Natural IgM and the Development of B Cell-Mediated Autoimmune Diseases. Physiol Behav. 2017;176(5):139–48.
33. Darwiche W, Gubler B, Marolleau JP, Ghamlouch H. Chronic lymphocytic leukemia B-cell normal cellular counterpart: Clues from a functional perspective. Front Immunol. 2018;9:683.
2. Wall S, Woyach JA. Chronic Lymphocytic Leukemia and Other Lymphoproliferative Disorders. Clin Geriatr Med. 2016;32(1):175–89.
3. Bautista D, Vásquez C, Ayala-Ramírez P, Téllez-Sosa J, Godoy-Lozano E, Martínez-Barnetche J, et al. Differential Expression of IgM and IgD Discriminates Two Subpopulations of Human Circulating IgM+IgD+CD27+ B Cells That Differ Phenotypically, Functionally, and Genetically. Front Immunol. 2020;11:736.
4. Lundell A-C, Johansen S, Adlerberth I, Wold AE, Hesselmar B, Rudin A. High Proportion of CD5 + B Cells in Infants Predicts Development of Allergic Disease . J Immunol. 2014;193(2):510–8.
5. Sindhava VJ, Bondada S. Multiple regulatory mechanisms control B-1 B cell activation. Front Immunol. 2012;372.
6. Reyneveld GI, Savelkoul HFJ, Parmentier HK. Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models . A Review. Front Immunol. 2020;11:2139.
7. Grönwall C, Silverman GJ. Natural IgM: Beneficial autoantibodies for the control of inflammatory and autoimmune disease. J Clin Immunol. 2014;34(SUPPL. 1):12–21.
8. Jazayeri MH, Pourfathollah AA, Rasaee MJ, Porpak Z, Jafari ME. The concentration of total serum IgG and IgM in sera of healthy individuals varies at different age intervals. Biomed Aging Pathol. 2013;3(4):241–5.
9. Rodriguez-Zhurbenko N, Quach TD, Hopkins TJ, Rothstein TL, Hernandez AM. Human B-1 cells and B-1 cell antibodies change with advancing age. Front Immunol. 2019;10(483):1–15.
10. Shao WH, Cohen PL. Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res Ther. 2011;13(1):1–7.
11. Cautivo KM, Molofsky AB. Regulation of metabolic health and adipose tissue function by group 2 innate lymphoid cells. Eur J Immunol. 2016;46(6):1315–25.
12. Morris G, Puri BK, Olive L, Carvalho AF, Berk M, Maes M. Emerging role of innate B1 cells in the pathophysiology of autoimmune and neuroimmune diseases: Association with inflammation, oxidative and nitrosative stress and autoimmune responses. Pharmacol Res. 2019;148(25):104408.
13. Bhat NM, Adams CM, Chen Y, Bieber MM, Teng NNH. Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34-Encoded Natural IgM Antibodies. J Immunol. 2015;195(11):5178–88.
14. Locke IC, Leaker B, Cambridge G. A comparison of the characteristics of circulating anti-myeloperoxidase autoantibodies in vasculitis with those in non-vasculitic conditions. Clin Exp Immunol. 1999;115(2):369–76.
15. Pugh-Bernard AE, Silverman GJ, Cappione AJ, Villano ME, Ryan DH, Insel RA, et al. Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest. 2001;108(7):1061–70.
16. Bhat NM, Bieber MM, Spellerberg MB, Stevenson FK, Teng NNH. Recognition of auto- and exoantigens by V4-34 gene encoded antibodies. Scand J Immunol. 2000;51(2):134–40.
17. Mangge H, Prüller F, Schnedl W, Renner W, Almer G. Beyond macrophages and T cells: B cells and immunoglobulins determine the fate of the atherosclerotic plaque. Int J Mol Sci. 2020;21(11):1–13.
18. Alugupalli KR, Leong JM, Woodland RT, Muramatsu M, Honjo T, Gerstein RM. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity. 2004;21(3):379–90.
19. Miles K, Simpson J, Brown S, Cowan G, Gray D, Gray M. Immune tolerance to apoptotic self is mediated primarily by regulatory B1a cells. Front Immunol. 2018;8(2):1–16.
20. Giltiay NV, Chappell CP, Clark EA. B-cell selection and the development of autoantibodies. Arthritis Res Ther. 2012;14(Suppl 4):1–13.
21. Ran Z, Yue-Bei L, Qiu-Ming Z, Huan Y. Regulatory B Cells and Its Role in Central Nervous System Inflammatory Demyelinating Diseases. Front Immunol. 2020;11(12):1–18.
22. Magatti M, Masserdotti A, Cargnoni A, Papait A, Stefani FR, Silini AR, et al. The role of b cells in pe pathophysiology: A potential target for perinatal cell-based therapy? Int J Mol Sci. 2021;22(7).
23. Hayakawa K, Formica AM, Brill-Dashoff J, Shinton SA, Ichikawa D, Zhou Y, et al. Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression. J Exp Med. 2016;213(13):3007–23.
24. Calvo J, Places L, Espinosa G, Padilla O, Vilà JM, Villamor N, et al. Identification of a natural soluble form of human CD5. Tissue Antigens. 1999;54(2):128–37.
25. Rovituso DM, Duffy CE, Schroeter M, Kaiser CC, Kleinschnitz C, Bayas A, et al. The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients. Sci Rep. 2015;5(9):1–8.
26. Tørring C, Petersen CC, Bjerg L, Kofod-Olsen E, Petersen T, Höllsberg P. The B1-cell subpopulation is diminished in patients with relapsing-remitting multiple sclerosis. J Neuroimmunol. 2013;262(1–2):92–9.
27. Aziz M, Holodick NE, Rothstein TL, Wang P. The role of B-1 cells in inflammation. Immunol Res. 2015;63(1–3):153–66.
28. Zhang X. Regulatory functions of innate-like B cells. Cell Mol Immunol. 2013;10(2):113–21.
29. Vyshkina T, Kalman B. Autoantibodies and neurodegeneration in multiple sclerosis. Lab Investig. 2008;88(8):796–807.
30. Fetter T, Niebel D, Braegelmann C, Wenzel J. Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases-Implications for Therapeutic Approaches. Cells. 2020;9(12).
31. Roudafshani Z, Jazayeri MH, Mahmoudi AR, Nedaeinia R, Safari E, Jazayeri A. Evaluation of the frequency of CD5+ B cells as natural immunoglobulin M producers and circulating soluble CD5 in patients with bladder cancer. Mol Biol Rep. 2019;46(6):6405–11.
32. Justyna W. Natural IgM and the Development of B Cell-Mediated Autoimmune Diseases. Physiol Behav. 2017;176(5):139–48.
33. Darwiche W, Gubler B, Marolleau JP, Ghamlouch H. Chronic lymphocytic leukemia B-cell normal cellular counterpart: Clues from a functional perspective. Front Immunol. 2018;9:683.
| Files | ||
| Issue | Vol 21 No 6 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i6.11527 | |
| Keywords | ||
| CD5 CD19 B cells Chronic lymphocytic leukemia Multiple sclerosis Natural IgM VH4-34 gene | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Pezeshki S, Jazayeri MH, Chahardouli B, Tajik N, Nabavi SM, Akbarzadeh M. Biological Features of CD5+ CD19+ B1 Cell and Natural IgM (VH4-34) in Chronic Lymphocytic Leukemia vs. Multiple Sclerosis. Iran J Allergy Asthma Immunol. 2022;21(6):670-676.
