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Expanded Population of Activated Antigen-Engaged Cells within the Naive B Cell Compartment of Patients with Systemic Lupus Erythematosus¹

Nan-Hua Chang^*, Tamara McKenzie^*, Gabriel Bonventi^*, Carolina Landolt-Marticorena^*, Paul R. Fortin^*,,, Dafna Gladman^*,,, Murray Urowitz^*,, and Joan E. Wither^2,*,,

^* Arthritis Centre of Excellence, Toronto Western Hospital Research Institute, Toronto Western Hospital and Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada; and Department of Medicine and Department of Immunology, University of Toronto, Toronto, Ontario, Canada

Polyclonal B cell activation is a well-described feature of systemic lupus erythematosus (SLE), but the immune mechanisms leading to this activation are unclear. To gain insight into these processes, we extensively characterized the activated peripheral blood B cell populations in SLE. PBMC from lupus patients and healthy controls were stained with various combinations of conjugated Ab to identify distinct peripheral B cell subsets, and activation was assessed by measurement of forward scatter and CD80 or CD86 expression using flow cytometry. SLE patients had altered proportions of several B cell subsets, many of which demonstrated increased activation as assessed by forward scatter. This activation occurred at an early developmental stage, as B cells in the transitional (T2) stage were already significantly larger than those seen in controls. Increased proportions of CD80- or CD86-expressing cells were also seen in multiple B cell subsets, with the most striking differences observed in the naive CD27^–CD23⁺ population. Within the CD23⁺ subset, increased costimulatory molecule expression was most pronounced in an IgD⁺IgM^low population, suggesting that activation follows Ag engagement. Although controls also had IgD⁺IgM^lowCD23⁺ cells, they were reduced in number and not activated. Thus, there is an altered response to Ig receptor engagement with self-Ags in lupus.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Canadian Institutes of Health Research (CIHR; to J.E.W). J.E.W. is the recipient of an Arthritis Society/CIHR Investigator Award. P.R.F. is the recipient of a combined The Arthritis Society/CIHR Institute of Musculoskeletal Health and Arthritis Investigator Award. N.-H.C. is the recipient of an Arthritis Centre of Excellence Fellowship.

² Address correspondence and reprint requests to Dr. Joan E. Wither, Departments of Medicine and Immunology, University of Toronto, 1E420, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. E-mail address: jwither{at}uhnres.utoronto.ca

³ Abbreviations used in this paper: SLE, systemic lupus erythematosus; BAFF, B cell-activating factor; T2, transitional type 2; SLEDAI-2K, SLE disease activity index-2K; FSC, forward scatter; int, intermediate; T1, transitional type 1; GC, germinal center.