Normal B cells express 51p1-encoded Ig heavy chains that are distinct from those expressed by chronic lymphocytic leukemia B cells.
51p1 is an allele of V(H)1-69 that frequently is expressed by chronic lymphocytic leukemia (CLL) B cells with little or no somatic mutation. The rearranged 51p1 genes expressed by CLL B cells have a distinctive use of D segments D3-3/DXP4 and D3-10/DXP'1, a favored use of J(H)6, and a longer third complementarity-determining region than the rearranged Ig genes used by CLL B cells that express V(H)1 genes other than V(H)1-69. We examined the 51p1-encoded Ig expressed by blood B cells of healthy donors. In contrast to the infrequent use of J(H)4 by 51p1-expressing CLL (e.g., 4%), 36% of the rearranged 51p1 sequences from normal blood B cells used J(H)4. Furthermore, the D segment use of the rearranged 51p1 sequences from normal blood B cells was not restricted, but reflected the D segment use of nonselected IgH of normal B cells. Finally, the mean length of the third complementarity-determining region for the 51p1 genes of normal blood B cells was 14.6 +/- 4.3 (SD) codons. This is significantly shorter than that noted for 51p1-expressing CLL B cells (18.8 +/- 3.2; p < 0.0001, n = 51). This study demonstrates that the 51p1-encoded IgH expressed in CLL are not representative of the 51p1-encoded IgH expressed by normal blood B cells, indicating that CLL B cells express IgH that are distinctive from those found in the normal adult blood B cell repertoire.
Widhopf
G F
GF
Division of Hematology/Oncology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Kipps
T J
TJ
D000328:Adult; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D019075:Electrophoresis, Capillary; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D014066:Palatine Tonsil; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region