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Ig and Heavy Chain Gene Usage in Early Untreated Systemic Lupus Erythematosus Suggests Intensive B Cell Stimulation¹

Department of Internal Medicine and The Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75235

To determine the distribution of V and J as well as V_H and J_H gene usage in a patient with systemic lupus erythematosus (SLE), productive and nonproductive VJ and V(D)J rearrangements were amplified from individual peripheral CD19⁺ B cells and were analyzed. No differences in the V and J or the V_H and J_H gene usage in the nonproductive gene repertoire of this SLE patient were found compared with the distribution of genes found in normal adults, whereas marked skewing of both V and V_H was noted among the productive rearrangements. The distribution of productive V rearrangements was skewed, with significantly greater representation of the J distal cluster C V genes and the V distal J7 element, consistent with the possibility that there was receptor editing of the V locus in this patient. Significant bias in V_H gene usage was also noted with V_H3 family members dominating the peripheral B cell repertoire of the SLE patient (83%) compared with that found in normal subjects (55%; p < 0.001). Notably, a clone of B cells employing the V_H3-11 gene for the heavy chain and the V1G segment for the light chain was detected. These data are most consistent with the conclusion that extreme B cell overactivity drives the initial stages of SLE leading to remarkable changes in the peripheral V gene usage that may underlie on fail to prevent the emergence of autoimmunity.

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