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ORIGINAL ARTICLE |
1 Institute of Pathology, University Medical Center Benjamin Franklin, The Free University of Berlin, 12200 Berlin, Germany
2 Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany
Correspondence to:
Dr M Hummel, Institute of Pathology, University Medical Center Benjamin Franklin, The Free University of Berlin, 12200 Berlin, Germany;
michael.hummel{at}medizin.fu-berlin.de
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.
Keywords: B lymphocytes; VH replacement; immunoglobulin gene rearrangement; antibodies
Abbreviations: FR, framework; Ig, immunoglobulin; IgH, immunoglobulin heavy chain; MALT, mucosa associated lymphoid tissue; PCR, polymerase chain reaction
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