Antibody Responses

AID mutant analyses indicate requirement for class-switch-specific cofactors. Ta, V.-T. et al. Nature Immunol. 10 August 2003 (DOI: 10.1038/ni964)

Activation-induced cytidine deaminase (AID) is known to be the only B-cell-specific factor required for both class-switch recombination (CSR) and somatic hypermutation (SHM) during the maturation of an antibody response. How then does AID differentially regulate these two processes? Honjo and colleagues show that this might be achieved by specific cofactors that regulate substrate interaction. Point mutations in the carboxy-terminal domain of AID abrogated CSR but did not affect SHM, which indicates the involvement of a CSR-specific cofactor that binds to the carboxyl terminus of AID.

B-Cell Development

The nonimmunoglobulin portion of λ5 mediates cell-autonomous pre-B cell receptor signaling. Ohnishi, K. & Melchers, F. Nature Immunol. 3 August 2003 (DOI: 10.1038/ni959)

Expression of the pre-BCR — composed of one rearranged heavy chain and a surrogate light chain (SLC; which is itself composed of VpreB and λ5) — is a crucial intermediate step in B-cell development, allowing B cells to proliferate in a ligand-independent manner. Deletion or mutation of the amino-terminal non-immunoglobulin region of λ5 led to increased cell-surface expression of the pre-BCR, but decreased pre-BCR aggregation and decreased phosphorylation of proteins in the pre-BCR complex. These results indicate that the amino-terminal region of λ5 is required for signal transduction by the pre-BCR in response to receptor crosslinking. No ligands or other cell types were added to the pre-B cells, so the authors propose that this crosslinking involves a linking factor produced by the pre-B cell itself or non-covalent interactions between two λ5 non-immunoglobulin regions.

Lymphocyte Migration

Cutting edge: the B cell chemokine CXC chemokine ligand 13/B lymphocyte chemoattractant is expressed in the high endothelial venules of lymph nodes and Peyer's patches and affects B cell trafficking across high endothelial venules. Ebisuno, Y. et al. J. Immunol. 171, 1642–1646 (2003)

The chemokines CC-chemokine ligand 21 (CCL21) and CCL19 are localized to high endothelial venules (HEVs) and are involved in controlling T-cell trafficking to lymph nodes or Peyer's patches. In this study, Ebisuno et al. analysed the role of the B-cell chemoattractant CXCL13 in the trafficking of B cells across HEVs. CXCL13 was found to be expressed on the luminal surface of HEVs. B-cell arrest in HEVs of Peyer's patches was impaired in CXCL13-deficient mice, but superfusion of the Peyer's patches with CXCL13 restored the expression of CXCL13 at the luminal surface and some B cells were once again able to adhere. This study shows that CXCL13 expressed by HEVs has a role in the trafficking of B cells in lymphoid organs.