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Lecture 29

MIMM 214 Lecture 29: Adaptive Immunity XII: Germinal Center, Somatic Hypermutation, Affinity Maturation, Class Switching

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Microbiology and Immun (Sci)
MIMM 214
Claire Trottier

Lecture 29 Monday, March 20, 2017 Lecture 28 content cont'd: Somatic hypermutation • Operates on activated B cells in peripheral lymphoid organs o In the germinal center of lymph nodes • High rate of point mutations in the V gene sequences that improve Ag binding • The mutations are selected for increased affinity for Ag - affinity maturation • This process also takes place during secondary or tertiary responses o Get higher affinity antibodies • Increasing affinity occurs in CDR domains in the V regions responsible for binding to the antigen • B cells go through somatic hypermutation again after subsequent exposures to the same antigen, increasing antibody affinity Class Switching • Only occurs after B cell activation • Irreversible • Requires class switch recombination guided by switch regions located upstream of each C gene • It requires: o AID = activation-induced cytidine deaminase on ssDNA o Other proteins • Together they drive DNA repair LECTURE 29: GERMINAL CENTER, SOMATIC HYPERMUTATION, AFFINITY MATURATION, CLASS SWITCHING Recall B Cell Activation • Option 1: form primary focus where the B cells release IgM/IgD antibodies that have a baseline affinity for the antigen • Secondary lymphoid follicle aka Germinal Centre • B cells undergo processes to produce antibodies that are more specific & effective o Somatic hypermutation o Affinity maturation o Class switching Germinal Center • Dark and light zones play different roles in the further maturation process of B cells, involved in somatic hypermutation and class switching • Follicular dendritic cells (FDCs) retain Ag in the light zone - much like SCS macrophages o They have lots of complement receptors on their surface – can bind and retain antigens that were opsonized by complement • Also have receptors specific for the Fc (constant) region of antibodies – thus can also bind antigens coated with antibodies What happens in the germinal centre? • B cells that first enter germinal centre o Have already encountered Ag (signal 1) and have been activated by a T cell at the B-T border (signal 2) o Have the ability to produce IgM/IgD of a baseline affinity • In the germinal centre: o Somatic hypermutation • Affinity for antigen improves o Class switching • From IgM/IgD to IgG or IgA or IgE • The Ag specificity is still the same Productive outcomes • Plasma cells o They stop expressing high levels of BCR o Secrete Ig of the same specificity as the BCR of the progenitor B cell o Should bind Ag with higher affinity o Secreted Ig can be IgG, IgA, IgE – but each plasma cell can only secrete one type • Memory B cells: o Express high levels of BCR o BCR has same specificity as progenitor B cell o BCR should have hig
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