The B Cell and Rheumatoid Arthritis Part II: Affinity Maturation of Antibodies, Unlucky Chance Event Leads to Autoantibody (Rheumatoid Factor), and Apoptosis Part II Page 37
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Affinity maturation and the chance event of the occurance of a rheumatoid factor is described.
Slide 1: "The B-cell and Affinity Maturation " 360 x 240 pixels 12kb drawn freehand in 3dStudio Max
Slide 2: "The B-cell makes Antibody #1 that Binds to an Antigen with a Given Affinity " 360 x 240 pixels 12kb drawn freehand in 3dStudio Max
Slide 3: "A Somatic Mutation leads to the Production of Antibody #2 with a Higher Affinity for Antigen" 360 x 240 pixels 15kb drawn freehand in 3dStudio Max
In brief, pathologic, self-sustaining autoantibodies are felt to develop spontaneously by accident. These deleterious events are made possible because the process of affinity maturation cannot be purposefully directed by the B-cell. Rather, somatic mutations occur randomly, and, under normal circumstances, mutations that lead to antibodies with reduced affinity for the non-self antigen, or antibodies that then react with self-antigen will lead to apoptosis of the responsible B-cells. There is both a T-cell and a B-cell effector mechanism for accomplishing this role. However, in Rheumatoid Arthritis, an unlucky chance event transpires and a B-cell begins producing an autoantibody, with IgG probably the most significant isotype, directed with high affinity to the Fc portion of IgG, i.e. a rheumatoid factor.
Slide 4: "Production of the Higher Affinity Antibody #2 leads to Survival of the Somatically Mutated B-cell " 360 x 240 pixels 16kb drawn freehand in 3dStudio Max
Slide 5: "Antibody #3 is Produced my Somatic Mutation and has a lower afffinity for antigen than Antibody #1 " 360 x 240 pixels 14kb drawn freehand in 3dStudio Max
Slide 6: "The Somatically Mutated B-cell making Antibody #3 Dies by Apoptosis " 360 x 240 pixels 13kb drawn freehand in 3dStudio Max
Slide 7: "By Chance, a Somatically mutated B-cell makes an Antibody to the Fc Portion of IgG, a Rheumatoid Factor " 360 x 240 pixels 17kb drawn freehand in 3dStudio Max
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