Characterisation of anergic B cells in a new mouse model with altered B cell receptor signalling

Zhang, Lingling (2019). Characterisation of anergic B cells in a new mouse model with altered B cell receptor signalling. University of Birmingham. Ph.D.

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Abstract

While the B cell antigen receptor (BCR) membrane IgM (mIgM) transmits signals via Igα/β, the cytoplasmic tail of mIgG is able to transmit signals directly. We have generated mice where the IgG1 cytoplasmic signalling tail was added to the C-terminus of IgM (IgMg1 mouse). During B cell development, IgMg1 B cells experience stronger negative selection resulting in tonic BCR signal transduction being repressed and reduced mIgM expression. BCR stimulation of immature and mature IgMg1 B cells results in reduced signalling. This shows that IgMg1 B cells leave the bone marrow as anergic cells.

IgMg1 B cells respond less efficiently to thymus-independent antigens. They do, however, respond well to the thymus-dependent antigen. The anergic pattern of IgMg1 B cells is maintained throughout the GC response and even after they become IgG switched memory B cells (MBCs). These effects may contribute to a delay in the shift of antigen-specificity of GC B cells.

These results are in line with recent studies showing that anergic B cells are licensed to participate in Germinal Centre (GC) reactions, where they can undergo clonal redemption. We conclude that IgMg1 mice are a new model to study anergy in B cells with a complete repertoire of BCR-specificities.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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