Ig λ and heavy chain gene usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation

To determine the distribution of Vλ and Jλ as well as V₁₁ and J₁₁ 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 Vλ and Jλ or the V₁₁ and J₁₁ 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 Vλ and V₁₁ was noted among the productive rearrangements. The distribution of productive Vλ rearrangements was skewed, with significantly greater representation of the Jλ distal cluster C VA genes and the Vλ distal Jλ7 element, consistent with the possibility that there was receptor editing of the Vλ locus in this patient. Significant bias in V₁₁ gene usage was also noted with V₁₁3 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 V₁₃-11 gene for the heavy chain and the Vλ1G 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.