RESEARCH - Regeneration of B cell subsets after transient B cell depletion using rituximab in RA

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Arthritis Rheum. 2006 Jul 25;54(8):2377-2386 [Epub ahead of print]

Regeneration of B cell subsets after transient B cell depletion using

anti-CD20 antibodies in rheumatoid arthritis.

Roll P, Palanichamy A, Kneitz C, Dorner T, Tony HP.

University of Wurzburg, Wurzburg, Germany.

OBJECTIVE: Transient B cell depletion with the monoclonal anti-CD20 antibody

rituximab has resulted in favorable clinical responses in patients with

rheumatoid arthritis (RA). However, little is known about the regeneration

profile of different peripheral B cell subpopulations. The aim of this study

was to delineate the regeneration profile of different B cell subsets in the

peripheral blood after selective anti-CD20-mediated B cell depletion.

METHODS: Seventeen patients with RA refractory to standard therapy were

treated with rituximab. Patients 1-6 received 4 weekly infusions of

rituximab at a dose of 375 mg/m(2), and patients 7-17 received 2 infusions

of rituximab (1,000 mg), 2 weeks apart. Four-color staining was performed at

several time points, using CD38, IgD, and CD27 in addition to other cell

surface markers. In one patient, the mutational status of the immunoglobulin

receptor was examined. RESULTS: The analysis revealed a distinct pattern of

B cell regeneration. The first wave of repopulating B cells were immature B

cells (CD38(high),IgD+,CD10+,CD24(high)), the immunoglobulin receptors of

which were not yet somatically mutated. In parallel, a recirculation of

plasma cells was observed. Later, the number of naive B cells increased, and

these cells predominated in the peripheral blood B cell pool. CD27+ memory B

cells showed a slow and delayed repopulation, and the level of these cells

stayed significantly reduced (<50%) compared with baseline values, for more

than 2 years.

CONCLUSION: Our findings provide evidence for a characteristic regeneration

pattern of B cell subpopulations, with long-lasting modulation of B cell

subset composition, after selective anti-CD20-mediated B cell depletion.

PMID: 16869000

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6869000

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