Rituximab therapy leads to reduced imprints of receptor revision in immunoglobulin κ and λ light chains

Arumugam Palanichamy, Khalid Muhammad, Petra Roll, Stefan Kleinert, Thomas Dörner, Hans Peter Tony

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Objective. Transient B cell depletion by rituximab (RTX) has become a specific treatment of rheumatoid arthritis (RA). Although phenotypic repopulation kinetics of B cell subsets are well documented, precise molecular analyses of the reconstituting immunoglobulin (Ig) genes encoding the B cell receptor in RA are sparse. Methods. A total of 708 individual CD19+CD27+ (memory) and CD19+CD27- (naive) B cells from 2 patients with RA were analyzed at baseline and 7 months after RTX at B cell repopulation. Ig light chain variable kappa (Vκ) and lambda (Vλ) light chain gene rearrangements were amplified, sequenced, and analyzed with a focus on receptor revision. Results. The naive as well as the memory repertoire repopulated polyclonally with diverse use of variable light chain gene families and minigenes. During the reconstitution phase, B cells used significantly fewer Jκ distal Vκ genes (p = 0.0006), with a higher frequency of somatic hypermutation of rearrangements employing Jκ5 compared to baseline in memory B cells. The use of Vλ rearrangements in regenerating B cells was also biased toward use of Vλ genes of the proximal cassette. In general, reemerging CD27+ Ig light chain genes were substantially more highly mutated than before RTX therapy (p < 0.0001, baseline vs during reconstitution). Conclusion. Our data indicate that RTX therapy leads to generation of distinct Vκ/Jκ and Vλ/Jλ gene repertoires consistent with replenishment of antigen-experienced B cells by germinal centers. At baseline, the imprints of receptor revision appeared to be more striking, which indicates that receptor revision is active in patients with RA and can be reduced by RTX. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)1130-1138
Number of pages9
JournalJournal of Rheumatology
Issue number6
Publication statusPublished - Jun 2012
Externally publishedYes


  • Immunoglobulin light chains
  • Receptor revision
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology


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