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Biomedical subjects

Jean-Claude Weill

Publications and source records attributed to Jean-Claude Weill.

23 records · Page 2Linked to original sources
PubMed2002

Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota.

Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed Vh/Vl genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an error-prone DNA synthesis step that introduces the mutations. The Y family of DNA polymerases--pol eta, pol iota, pol kappa and rev1--are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template. By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota.

Antibody Affinity↗
PubMed2002

AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line.

Immunoglobulin (Ig) gene hypermutation can be induced in the BL2 Burkitt's lymphoma cell line by IgM cross-linking and coculture with normal or transformed T helper clones. We describe here a T cell#150;independent in vitro induction assay, by which hypermutation is induced in BL2 cells through simultaneous aggregation of three surface receptors: IgM, CD19 and CD21. The mutations arise as a post-transcriptional event within 90 min. They are stably introduced in the G1 phase of the cell cycle, occurring in one of the two variable gene DNA strands, and eventually become fixed by replication in one of the daughter cells. Inactivation of AID (activation-induced cytidine deaminase) by homologous recombination in BL2 cells completely inhibits the process, thus validating this induction procedure as a model for the in vivo mechanism.

Burkitt Lymphoma↗
PubMed2002

Cutting edge: DNA polymerases mu and lambda are dispensable for Ig gene hypermutation.

Mutations arising in Ig V genes during an immune response are most likely introduced by one or several error-prone DNA polymerases. Many of the recently described nonreplicative DNA polymerases have an intrinsic fidelity compatible with such an activity, the strongest candidates being polymerase (pol) eta, pol iota, pol zeta, and pol mu. We report in this work that mice inactivated for either of the two polymerases related to pol beta (i.e., pol mu and pol lambda) are viable and fertile and display a normal hypermutation pattern.

Animals↗