ECTOPIC GERMINAL CENTER REACTION IN SYSTEMIC LUPUS

University Of Texas Sw Med Ctr/Dallas, Dallas TX

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Adapted from the Investigator's abstract): Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and widespread immunologic abnormalities, the most relevant of which are hypergammaglobulinemia, immune complex formation, and complement system activation. Highly specific autoantigen-driven responses, particularly those directed at protein and nucleic acid components of intracytoplasmic and intranuclear particles, are characteristic of SLE patients. At the peak of disease activity and antibody secretion, however, SLE patients are known to display peripheral blood lymphopenia. The investigator's laboratory has previously described methods to isolate human peripheral B cell subpopulations. Now they show that the peripheral blood B cells of children with SLE differ from healthy adults and children. In particular, the conventional recirculating naive B cell pool is decreased in children with SLE, while B cells with pre-germinal center phenotype are expanded. Consistent with this information, genes restricted to the germinal center (GC) reaction can be amplified from SLE peripheral B cells. Additionally, a cell population that co-purifies with B cells but lacks the pan-B cell markers CD19 and CD20 is expanded in these patients. This population is composed of a CD79a+ B cell subset, and a CD79a- (dendritic cell?) subset. These data lead the investigators to propose that an ectopic and accelerated GC reaction takes place in SLE. The experiments described below are designed to test their hypothesis and to gain understanding of the nature of B cell alteration(s) in SLE. The aims of the current application are: 1. To further demonstrate that the IgD+ CD38+ population + _ expanded in the blood of SLE patients corresponds to pre-GC cells. 2. To + _ characterize the phenotype and function of the recirculating B cell subpopulation(s) expressing surface CD40-L in SLE blood. 3. To identify the + _ nature and function of the SLE-restricted CD19- CD20- cell populations that co-purify with B cells. 4. To determine the clinical relevance of the + _ accumulation f IgD+ CD38+ B cells and/or CD19- CD20- cells.