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Peripheral Regulatory B Cell Phenotype in Multiple Sclerosis Patients

Jakob G. Habib, Jiusheng Deng, Andrea Pennati, Neil S. Lava, Jacques Galipeau

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Abstract

Abstract Abstract 4843 Regulatory B cells (Bregs) are a unique CD5+/CD1d+/IL10+ B cell subtype which has novel immunosuppressive capabilities. It remains to be determined if subjects suffering from autoimmune ailments such as multiple sclerosis (MS) display a defect in number or function of Bregs in association with their disease. Our hypothesis is that total B cell number, and Breg subset in particular, is distinct when comparing peripheral blood B cell populations from MS to healthy controls (HC). This study herein focuses on establishing a phenotypic baseline of the peripheral B cell profile. The total number of CD19+ B cells in HC is 892±816 cells/μL (average ±SD, n=28), of which CD5+/CD1d+ Breg subset is 4.6±5.6 cells/μL. We found a greater number of B cells in MS subjects, 1441±1011 cells/μL (n=22, p<0.05, Student's t-test). However, the number of Bregs in MS patients is not significantly different from HC, 7.5±7.6 cells/μL (p=0.13). We further interrogated the phenotype of B cells in MS subjects and found that there is an increased number of CD27−IgD+ naïve/intermediate phenotype in MS, 1041±794 cells/μL, versus HC, 624±606 cells/μL (p<0.05). Our findings demonstrate that MS is not associated with a deficiency in the absolute number of CD5+/CD1d+ Bregs but rather a 60% increase in CD27−IgD+ B cells. We hypothesize that altered B cell distribution may be functionally associated to the underlying immune disease process of MS. This finding may inform the design of clinical trials examining B cell depletion strategies for treatment of MS. Disclosures: No relevant conflicts of interest to declare.

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Abstract Abstract 4843 Regulatory B cells (Bregs) are a unique CD5+/CD1d+/IL10+ B cell subtype which has novel immunosuppressive capabilities. It remains to be determined if subjects suffering from autoimmune ailments such as multiple sclerosis (MS) display a defect in number or function of Bregs in association with their disease. Our hypothesis is that total B cell number, and Breg subset in particular, is distinct when comparing peripheral blood B cell populations from MS to healthy controls (HC). This study herein focuses on establishing a phenotypic baseline of the peripheral B cell profile. The total number of CD19+ B cells in HC is 892±816 cells/μL (average ±SD, n=28), of which CD5+/CD1d+ Breg subset is 4.6±5.6 cells/μL. We found a greater number of B cells in MS subjects, 1441±1011 cells/μL (n=22, p<0.05, Student's t-test). However, the number of Bregs in MS patients is not significantly different from HC, 7.5±7.6 cells/μL (p=0.13). We further interrogated the phenotype of B cells in MS subjects and found that there is an increased number of CD27−IgD+ naïve/intermediate phenotype in MS, 1041±794 cells/μL, versus HC, 624±606 cells/μL (p<0.05). Our findings demonstrate that MS is not associated with a deficiency in the absolute number of CD5+/CD1d+ Bregs but rather a 60% increase in CD27−IgD+ B cells. We hypothesize that altered B cell distribution may be functionally associated to the underlying immune disease process of MS. This finding may inform the design of clinical trials examining B cell depletion strategies for treatment of MS. Disclosures: No relevant conflicts of interest to declare.

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Available abstract

Abstract Abstract 4843 Regulatory B cells (Bregs) are a unique CD5+/CD1d+/IL10+ B cell subtype which has novel immunosuppressive capabilities. It remains to be determined if subjects suffering from autoimmune ailments such as multiple sclerosis (MS) display a defect in number or function of Bregs in association with their disease. Our hypothesis is that total B cell number, and Breg subset in particular, is distinct when comparing peripheral blood B cell populations from MS to healthy controls (HC). This study herein focuses on establishing a phenotypic baseline of the peripheral B cell profile. The total number of CD19+ B cells in HC is 892±816 cells/μL (average ±SD, n=28), of which CD5+/CD1d+ Breg subset is 4.6±5.6 cells/μL. We found a greater number of B cells in MS subjects, 1441±1011 cells/μL (n=22, p<0.05, Student's t-test). However, the number of Bregs in MS patients is not significantly different from HC, 7.5±7.6 cells/μL (p=0.13). We further interrogated the phenotype of B cells in MS subjects and found that there is an increased number of CD27−IgD+ naïve/intermediate phenotype in MS, 1041±794 cells/μL, versus HC, 624±606 cells/μL (p<0.05). Our findings demonstrate that MS is not associated with a deficiency in the absolute number of CD5+/CD1d+ Bregs but rather a 60% increase in CD27−IgD+ B cells. We hypothesize that altered B cell distribution may be functionally associated to the underlying immune disease process of MS. This finding may inform the design of clinical trials examining B cell depletion strategies for treatment of MS. Disclosures: No relevant conflicts of interest to declare.

Key concepts: Regulatory B cells, CD19, Immunology, CD5, Immunoglobulin D, B cell, CD1D, Interleukin 10

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