Investigating the Production of Auto – Antibodies at Different Stages of B Cell Development

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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that is associated with the production of anti -nuclear autoantibodies. The production of class switched IgG autoantibodies is important in the pathology of the disease. Understanding autoantibody production and the mechanism by which these B cells escape from tolerance is crucial in studying SLE. Recently, a study showed that similar to mature B-cells, immature B-cell also undergo class switch recombination(CSR) and express the enzyme activation-induced cytidine deaminase (AID) which is required for CSR. Based on this result, it could be suggested that anti-nuclear IgG autoantibodies are produced at early B-cell development. To test this hypothesis, an auto-immune mouse model, 564Igi-AIDtg is used to determine the developmental stage at which class switched autoantibodies are produced. The 564Igi mouse has an anti-RNA antibody gene knocked-in the immunoglobulin (Ig) heavy and light gene loci. These mice are on an AID-deficient background and contain an inactive GFP-AID transgene where AID is only functional once GFP gene is excised by cre recombinase. Since CD21 B-cell surface marker is expressed on mature B-cells, while CD19 is expressed throughout B-cell development, by crossing the 564Igi-AIDtg with a cre+ mouse where the cre recombinase is under the CD21 or CD19 promoter, AID can be expressed in different B-cell stages. My results show that most of the 564Igi CD21cre unlike the 564Igi CD19cre mice do not have RNA binding antibodies and do not make antibody staining nucleoli. This observation suggests that immature B cells make class switched anti-RNA and idiotype positive IgG2a and IgG2b self -reactive antibodies.
A thesis submitted to the Department of Clinical Microbiology, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, in partial fulfillment of the requirements for the degree of Master of Science in Clinical Microbiology.