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Cutting Edge: TCR Gene Is Frequently Rearranged in Adult B Lymphocytes ¹

Ondrej Krejci^*,, Zuzana Prouzova^*, Ondrej Horvath, Jan Trka^*, and Ondrej Hrusak^2,*,

^* Childhood Leukemia Investigation Prague, and 2nd Department of Pediatrics and Institute of Immunology, Charles University 2nd Medical School, Praha, Czech Republic; and Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic

TCR gene rearrangement generates diversity of T lymphocytes by V(D)J recombination. Ig genes are rearranged in B cells using the same enzyme machinery. Physiologically, TCR gene is postulated to rearrange exclusively in T lineage, but malignant B precursor lymphoblasts contain rearranged TCR genes in most patients. Several mechanisms by which malignant cells break the regulation of V(D)J recombination have been proposed. In this study we show that incomplete TCR rearrangements V2-D3 and D2-D3 occur each in up to 16% alleles in B lymphocytes of all healthy donors studied, but complete VDJ rearrangement was negative at the sensitivity limit of 1%. Data are based on real-time quantitative PCR validated by PAGE and sequencing of the cloned products. Therefore, TCR genes rearrange not exclusively in T lineage. This study opens up further questions regarding the exact extent of the "cross-lineage" TCR or Ig rearrangements in normal lymphocytes, specific subsets in which the cross-lineage rearrangements occur, and the physiological importance of these rearrangements.

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