Normal B Cells Express 51p1 -Encoded Ig Heavy Chains That Are Distinct From Those Expressed by Chronic Lymphocytic Leukemia B Cells

Abstract

51p1 is an allele of VH1-69 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 JH6, and a longer third complementarity-determining region than the rearranged Ig genes used by CLL B cells that express VH1 genes other than VH1-69. We examined the 51p1-encoded Ig expressed by blood B cells of healthy donors. In contrast to the infrequent use of JH4 by 51p1-expressing CLL (e.g., 4%), 36% of the rearranged 51p1 sequences from normal blood B cells used JH4. 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.