Using BASP1 as a reporter of affinity matured plasma cells

A germinal centre B cell specific reporter mouse
Vaccination and infection lead to activation of B cells and differentiation of memory B cells as well as plasma cells that will produce neutralizing antibody in the long term. Initially, B cells are low affinity for antigen and will form low affinity extrafollicular plasma cells and antibody. Activated B cell re-entering B cell follicles form germinal centres - microenvironments where antigen-specific B cells expand, mutate their antibody genes and higher affinity B cell variants get selected on local antigen deposits. This will lead to the generation of high affinity memory and plasma cells producing high affinity antibody, leading to long term immunity. The same process is utilized in industry to generate high affinity antibody to specific antigens, which can generate monoclonal antibody drugs.
In collaboration with MedImmune, we generated a mouse that expresses Cre recombinase under the control of a gene with germinal centre B cell specific expression. This new mouse model has now been established at UoB. We plan to characterize expression in vivo using reporters of Cre recombinase such as Cre inducible fluorescent proteins. If Cre expression is faithful to germinal centre phenotype, we will use the model to isolate and characterize germinal centre B cells and descendants of the germinal centre response, i.e. high affinity long-lived plasma cells or memory B cells. Further, the new mouse model will be used to characterize the migration of germinal centre derived cells such as memory B cells. The model, after crossing the Cre expresser onto mice carrying inducible diphtheria toxin receptor, will further be used to target germinal centre derived memory B cells and plasma cells in order to test how much these cells contribute to long-term immunity.

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