Immunoglobulin Light Chain Usage Is Not Random in B-Cell Non-Hodgkin Lymphomas
LR Wolgast, Q Xie, F Sen, P Bhattacharyya, T Selvaggi, H Xu, D Xu, M Pathan, Q Hu, J Bang, X Xue, J Pizzolo, H Ratech. Montefiore Medical Center, Bronx, NY; New York University Medical Center, New York, NY; Hackensack University Medical Center, Hackensack, NJ; Boston University Medical Center, Boston, NY; Creighton University Medical Center, Omaha, NE; Albert Einstein College of Medicine, Bronx, NY
Background: During allelic exclusion, an individual B-cell expresses only one immunoglobulin light chain (IgL), either kappa (κ) or lambda (λ). If neoplastic transformation of a particular B-cell was random, one would expect that the κ/λ ratios of the various B-cell non-Hodgkin lymphoma (B-NHL) subtypes would be the same as any population of reactive B-cells. In order to investigate the potential role of allelic exclusion in lymphomagenesis, we studied a large κ/λ dataset of B-NHLs, reactive lymph nodes and tonsils.
Design: We collected flow cytometry κ/λ data from lymph nodes with either reactive lymphoid hyperplasia (RLH; N=736) or B-NHL (N=464) from five tertiary care medical centers. In addition, we analyzed κ/λ ratios in 35 reactive tonsils for B-cell subsets: Naive, CD38-, IgD+ ; germinal center, CD38+, IgD- ; memory, CD38-, IgD- ; and CD5+ B-cell, CD5+, CD19+.
Results: The ratio of κ-positive to λ-positive cases was significantly different among the various B-NHL subtypes (p=0.005, χ2). The dendrogram shows, from top to bottom, an increasing κ to λ ratio for B-NHL cases that parallels their presumed normal equivalent phenotype from naive to germinal center to memory B-cell (Figure 1). We did not find any differences among the κ/λ ratios of RLH in lymph nodes (1.37 ± 0.41) and B-cell subsets in tonsil (p=0.111, one-way ANOVA).
Conclusions: Our κ/λ data suggest that IgL usage is not random in B-NHLs. Although some preferences among IgL families have been reported, such as interaction with bacterial surface proteins by κ and autoantibody silencing by λ, the functional significance of a particular IgL remains largely unknown. We speculate that either environmental antigenic selection and/or intrinsic differences in κ or λ gene rearrangement could explain non-random κ or λ expression among B-NHL subtypes.
Monday, March 22, 2010 11:00 AM
Platform Session: Section B, Monday Morning