Abnormalities in peripheral B cell memory of patients with primary Sjogren's syndrome

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Arthritis Rheum. 2004 Jun;50(6):1897-908.

Abnormalities in peripheral B cell memory of patients with primary

Sjogren's syndrome.

Hansen A, Gosemann M, Pruss A, Reiter K, Ruzickova S, Lipsky PE, Dorner

T.

Department of Medicine/Outpatients' Department, Charite University

Hospital, Berlin, Germany. arne.hansen@...

OBJECTIVE: To delineate disturbances in peripheral B cell memory in

primary Sjogren's syndrome (SS). METHODS: Isotype-specific

immunoglobulin (Ig) heavy-chain transcripts were analyzed in

single-sorted CD19+,CD27- naive and CD19+,CD27+ memory B cells from

patients with primary SS and normal healthy control subjects. RESULTS: A

significantly higher frequency of B cells expressing mu-, alpha-, and/or

gamma-chain transcripts were found in patients with primary SS compared

with controls (58.0% versus 14.3%; P < 0.0001). Notably, 30.5% of

individual B cells (for primary SS, 38.7%; for controls, 12.7% [P <

0.0001]) simultaneously expressed transcripts for different Ig

heavy-chain isotypes using identical V(H)-D-J(H) rearrangements.

However, these cells lacked surface expression of more than one of the

respective Ig heavy-chain isotypes as well as messenger RNA (mRNA)

transcripts for 2 germinal center markers, activation-induced cytidine

deaminase, and Bcl-6. In contrast with the findings in normal healthy

controls, peripheral B cell memory in patients with primary SS was

characterized by 1) circulating CD27+ B cells expressing heavily mutated

Ig V(H) transcripts (mutational frequency 8.6% versus 4.3%; P < 0.0001),

2) significantly enhanced mutational frequencies of C mu transcripts

(9.6% versus 2.5%; P < 0.0001), 3) a high proportion (61.2%) of CD27+ B

cells expressing transcripts for multiple Ig heavy-chain isotypes, and

4) a CD27- memory-type B cell subpopulation expressing mutated C mu

transcripts.

CONCLUSION: Altogether, both B cell hyperactivity and striking

abnormalities in peripheral B cell memory are indicated at the

single-cell mRNA level in patients with primary SS. Detection of

multiple Ig heavy-chain transcripts in peripheral CD19+,CD27+ memory B

cells of patients with SS may represent the abnormal retention of

pre-switch mRNA transcripts in circulating post-switch B cells.

PMID: 15188366

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