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 4
9G4 cells are normally censored at the GC founder stage. (A) The left dot plot is representative of normal tonsils, demonstrating a prominent GC founder population (fraction e). As shown in the dot plot on the right, even in these tonsils, 9G4 B cells fail to progress past the pre-GC compartment and are scarce among GC founders. (B) Tonsils were analyzed for the expression of developmental markers CD10, CD44, and CD27 on conventional Bm1–Bm5 subsets (fractions a, b, f, and g). Pre-GC/Bm2′ cells were further divided into 3 fractions (c–e), with e containing the putative GC founders. As shown in the corresponding histograms, CD10 (a GC marker) was progressively acquired in fractions c–f, while CD44 (a marker downregulated in GC) was progressively lost. CD27 also experienced progressive upregulation in fractions c–f. Strikingly, the highest expression of the nuclear proliferation protein Ki67 was observed in fraction e. These results are consistent with fraction e representing GC founders undergoing the initial phases of clonal expansion. Importantly, the majority of 9G4 B cells was lost during pre-GC progression, greatly underrepresented among GC founders, and failed to expand within the GC, where their frequency continued to decline. (C) The scarce 9G4 B cells present within the GC founder and GC compartments were further analyzed for intracellular Ki67 expression. Consistent with their inability to form productive GC reactions, and in contrast to total B cells within these fractions, 9G4 B cells expressed very low levels of Ki67.