Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus
J. Clin. Invest. Amedeo Cappione, et al. 115:3205 doi:10.1172/JCI24179 [Go to this article.]

Figure 5
9G4 GCs are present in SLE patients at high frequency. (A) SLE tonsil biopsies stained with anti-IgD (left). Mature GCs formed by expansions of 9G4 cells were frequently identified in SLE. The upper row of the enlarged images depicts a typical mature 9G4⁺ proliferative GC with a well-formed FDC network (CD23/FDC) and positive Ki67 staining. The lower row shows similar findings by immunofluorescence: follicular mantle (IgD-PE, red), GC (CD38–7-aminomethylcoumarin, blue), and 9G4 (Alexa 488, green). (B) Representative example of a 9G4⁺ GC in an SLE spleen shown by 3-color immunofluorescence. (C) SLE GC showing the expansion of both 9G4 and LC1 B cells. (D) Healthy tonsils stained by immunofluorescence: IgD (red), Ki67 (blue), and either 9G4 or LC1 (both green). In contrast to SLE, healthy tonsils lack 9G4⁺ GC. Yet proliferating LC1 GCs were readily demonstrated. (E) A representative field from healthy spleens demonstrating the absence of 9G4 staining in the GCs is shown on the left. These results were routinely corroborated by immunofluorescence (middle panels). The photograph on the right illustrates the absence of 9G4 B cells from the GC and their accumulation within the FO and the MZ. (F) Enzymatic staining of serial sections obtained from tonsil biopsies of patients with RA failed to demonstrate 9G4⁺ GCs. Instead, as in healthy subjects, 9G4 B cells were restricted to the follicular mantle. In contrast, LC1⁺ GCs were readily identified in these patients.