K. Stamatopoulos et al., Selection of immunoglobulin diversity gene reading frames in B cell lymphoproliferative disorders, LEUKEMIA, 13(4), 1999, pp. 601-604
Assembly of immunoglobulin (Ig) heavy (H) variable (V), diversity (D) and j
oining (J) gene segments constitutes an important determinant of commitment
to the B cell lineage. The randomly selected D gene segment of a given VDJ
complex can potentially be found in all three possible reading frames (RFs
). In the present study, we examined the distribution of D gene RF in 'imma
ture' and 'mature' B cell lymphoproliferative disorders (BCLD). We analyzed
the clonotypic VDJ junctional sequences of our previously reported cases o
f follicular lymphoma (FL), as well as bcl-2/IgH junctions with recognized
D elements, A marked under-representation of RF1 was observed, with almost
equal usage of RF2 and RF3. A literature search for VDJ published sequences
in various BCLD identified a similar pattern of D gene RF usage in multipl
e myeloma (MM), with marked predilection for RFs 2 and 3, In B cell chronic
lymphocytic leukemia (B-CLL), the pattern of D-RF was 25% for RF1, 46% for
RF2 and 29% for RF3, while in B cell precursor acute lymphoblastic leukemi
a (precursor-B-ALL) all three RFs were used with similar frequencies. The m
arked under-representation of RF1 in FL and MM clonogenic rearranged D gene
s suggests selection on the basis of antigenic properties, possibly due to
constraints in forming a flexible loop within CDR3. In contrast, the more e
ven distribution of D-RF usage in B-CLL and precursor-B-ALL suggests that,
for these disorders, transformation of a immature type B cell repertoire ha
s occurred.