IgHV

IGHV stands for immunoglobulin heavy chain variable region. It comprises the set of variable-region gene segments of the immunoglobulin heavy chain (IGH). In humans these segments are located in the IGH locus on chromosome 14 and are organized into multiple Families designated by IGHV1, IGHV2, etc, with dozens of V genes and many alleles. During B cell development, a single IGHV gene segment is rearranged with one of 27- or more D and J segments through V(D)J recombination to form the variable region of the heavy chain. The resulting rearranged V region is joined to the constant region via RNA processing to produce a functional heavy chain that pairs with a light chain to form the B cell receptor or antibody.

Following antigen exposure, somatic hypermutation introduces point mutations in the IGHV region, allowing affinity maturation. Class switch recombination changes the constant region, altering effector function but not antigen specificity.

IGHV gene usage and mutation status are used diagnostically in certain B-cell cancers, most notably chronic lymphocytic leukemia and small lymphocytic lymphoma. In CLL, IGHV sequences are grouped as mutated (diverged from germline by ≥2–3%) or unmutated; mutated IGHV corresponds to a more favorable prognosis and longer survival, whereas unmutated is associated with poorer outcomes. IGHV status is determined by sequencing and comparing to germline IGHV alleles in databases such as IMGT.

Beyond clinical prognosis, IGHV repertoire analysis informs studies of immune responses, vaccine development, and B cell differentiation, with researchers examining germline variation, allele frequency, and biased V gene usage.

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