The role of CC-chemokine receptor-like 2 in the B cell response

Cook, Sarah Louise (2015). The role of CC-chemokine receptor-like 2 in the B cell response. University of Birmingham. Ph.D.

Preview

Cook15PhD.pdf
PDF - Accepted Version
Download (5MB)

Abstract

CCRL2 is a member of the atypical chemattractant family. It has been proposed to bind the chemokines CCL19 and CCL5, as well as the adipokine chemerin. Unlike typical chemokine receptors, atypical chemoattractant receptors do not undergo conventional G protein signalling upon binding, but instead degrade, transcytose or present their ligands on the cell surface. This study aims to characterise the role of CCRL2 in B cells upon their activation and differentiation into either extrafollicular plasmablasts or germinal centre B cells.

CCRL2 mRNA is upregulated upon plasmablast differentiation. Upon immunisation with NP-Ficoll, CCRL2 deficient mice produce more NP-specific antibody and larger numbers of NP-specific plasmablasts. Further assessment show this phenotype is due to B cell intrinsic effects. CCRL2 deficient plasmablasts tend to proliferate more and undergo less apoptosis than CCRL2 expressing plasmablasts.

The role of CCRL2 in the germinal centre was also assessed. Germinal centres formed normally, including polarisation into light and dark zones in CCRL2 deficient mice. However, FDCs within the germinal centre appeared to extend further into the follicular mantle in CCRL2 deficient mice. This may be the cause of an increased proportion of germinal centres over the whole spleen in CCRL2 deficient mice. These differences did not result in significant changes in affinity maturation.

Together, this shows a novel role for CCRL2 in the regulation of the extrafollicular plasmablast response to NP-Ficoll. However, minor differences in CCRL2 deficient germinal centres do not affect high affinity plasma cell output, suggesting a minimal role of CCRL2 in GC function.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):