TY - JOUR T1 - Receptor revision of immunoglobulin heavy chain genes in human MALT lymphomas JF - Molecular Pathology JO - Mol Pathol SP - 249 LP - 255 DO - 10.1136/mp.56.5.249 VL - 56 IS - 5 AU - D Lenze AU - A Greiner AU - C Knörr AU - I Anagnostopoulos AU - H Stein AU - M Hummel Y1 - 2003/10/01 UR - http://mp.bmj.com/content/56/5/249.abstract N2 - Background/Aims: Rearrangement of immunoglobulin gene segments, leading to B cells with functional receptors, is thought to be largely restricted to developing immature B cells in bone marrow. However, accumulating evidence suggests that mature B cells occasionally modify their antigen specificity by VH segment replacements during the germinal centre reaction to enhance antigen affinity, or to overcome self reactive antigen receptors. Although malignant B cells maintain the features of their normal counterparts in most instances, to date, such replacements have not been described for human B cell lymphomas. Methods: Rearranged immunoglobulin heavy chain genes from two extranodal marginal zone B cell lymphomas were amplified, cloned, and sequenced. Sequences with identical CDR3 regions were selected and aligned to each other and public databases. Results: VH replacements were seen in two extranodal marginal zone B cell lymphomas. In line with the hypothesis that in mature B cells these replacements are associated with active somatic hypermutation, in addition to VH replacement, different mutation patterns were seen in the revised VH portions. In the remaining common 3′-VH regions, these mutations could be used to establish a phylogenetic relation between the sequences, rendering the possibility of artefactual chimaeric polymerase chain reaction products very unlikely. Conclusions: These results support the view that VH replacements are a further mechanism for reshaping antigen affinity and specificity, and indicate that these receptor modifications are not restricted to normal and reactive germinal centre B cells, but may also occur in close association with the development of malignant B cell lymphomas. ER -