Class switch recombination, gene conversion, and somatic hypermutation that diversify rearranged Ig genes to produce various classes of high affinity Abs are dependent on the enzyme activation-induced cytosine deaminase (AID). Evidence suggests that somatic hypermutation is due to error-prone DNA repair that is initiated by AID-mediated deamination of cytosine in DNA, whereas the mechanism by w...

A key event in the pathogenesis of asthma and allergies is the production of IgE antibodies. We show here that IgE(+) cells were exceptional because they were largely found outside germinal centers and expressed, from very early on, a genetic program of plasma cells. In spite of their extragerminal center localization, IgE(+) cells showed signs of somatic hypermutation and affinity maturation. ...

Like Ig genes, TCR genes are formed by somatic rearrangements of noncontiguous genomic V, J, and C regions. Unlike Ig genes, somatic hypermutation of TCR V regions is an infrequent event. We describe the occurrence of spontaneous hypermutation in a nonproductively rearranged TCR alpha-chain gene in a clonal T cell hybridoma that had lost its productively rearranged alpha-chain. The mutating hyb...

It is generally accepted that in the maturation of an immune response, the quality of the antibody, as well as the quantity, will improve with time after immunization. In the mouse system, immunoglobulin obtained in the first days after immunization with NP-CGG showed greater specificity to NIP-CGG (heteroclitic specificity). While the specificity to the immunizing antigen (homoclitic specifici...

The development of memory B cells takes place in germinal centers (GC) of lymphoid follicles where antigen-driven lymphocytes undergo somatic hypermutation and affinity selection, presumably under the influence of helper T cells. However, the mechanisms that drive this complex response are not well understood. We explored the relationship between GC formation and the onset of hypermutation in r...

Somatic hypermutation (SHM) and class switch recombination (CSR) allow B cells to make high affinity antibodies of various isotypes. Both processes are initiated by activation-induced cytidine deaminase (AID) to generate dG:dU mismatches in the immunoglobulin genes that are resolved differently in SHM and CSR to introduce point mutations and recombination, respectively. The MutL homolog MLH3 ha...

Sharks possess the four canonical T-cell receptor (TCR) chains known from other vertebrates: α, β, γ, and δ. The loci encoding these chains employ recombination-activating gene (RAG)mediated somatic cell V(D)J rearrangement mechanisms for diverse repertoires. Sharks have some additional immunogenetic TCR capacity, including the doubly rearranging NAR-TCR δ, somatic hypermutation, and trans-rear...