CLL-Stereotyped Immunoglobulin Gene Rearrangements in Normal B-Cell Subsets
Posted: Monday, March 30, 2020
Chronic lymphocytic leukemia (CLL)-biased stereotyped immunoglobulin rearrangements (CBS-IG) have been found to represent a small portion of the B-cell receptor (BcR) inventory in healthy B cells, according to an immunogenetic study published in Molecular Medicine. The study is reportedly the first to address CBS-IG in normal B cells via modern sequencing. According to Monica Colombo, PhD, and colleagues of San Martino Hospital, Genova, Italy, “The different relative representation of CBS-IG in normal B cell subgroups suggests the requirement for additional selective processes before a full transformation into CLL is achieved.”
A total of six spleens free of neoplastic cells were acquired from San Martino Hospital, and three peripheral blood samples were acquired from healthy donors at the University of Genoa. Spleen samples were separated into nine different subsets of cells, whereas peripheral blood samples were sorted into CD5-positive and CD5-negative cells. The researchers used next-generation sequencing to obtain cDNA sequences of BcR immunoglobulin gene rearrangements. Bioinformatics and statistical evaluation was used to identify the distribution of CLL stereotypes.
The authors found CBS-IG represents 0.26% of IGHV1 genes of sampled splenic and peripheral blood B cells. However, the distribution of CBS-IG favors splenic and circulating CD5-positive (.57%) over CD5-negative cells (.17%). Mutation analysis revealed that the clear majority of CBS-IG in healthy spleen and peripheral blood was unmutated (92.1%). However, most switched memory B cells and double-negative B cells contained mostly mutated sequences, 87.5% and 50%, respectively. Lastly, the authors identified that normal B cells display a different CLL subset distribution of IGHV1 than those of CLL.
Disclosure: The study authors reported no conflicts of interest.
