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Differential Expression of the Inhibitory IgG Fc Receptor FcRIIB on Germinal Center Cells: Implications for Selection of High-Affinity B Cells

Sambasiva P. Rao, Kalpit A. Vora, and Tim Manser. Differential Expression of the Inhibitory IgG Fc Receptor FcRIIB on Germinal Center Cells: Implications for Selection of High-Affinity B Cells. The Journal of Immunology, 2002, 169: 1859–1868 .

The Journal received the following letter requesting correction of this article, which was published in the August 15, 2002 issue:

The authors would like to alert the scientific community to the fact that we have been unable to reproduce one of the findings presented in this manuscript. In Fig. 5B of this manuscript we showed the results of flow cytometric studies designed to measure the levels of surface expression of FcRIIB on splenic germinal center (GC) B cells (defined as B220⁺, IgD^–, GL7⁺) as compared with splenic non-GC B cells (defined as B220⁺, IgD⁺, GL7^–) using the anti-FcRIIB mAb K9.361. These cells were isolated from C57BL/6 mice that had been immunized i.p. 8 days earlier with 3 x 10⁸ sheep RBC (SRBC) per mouse. Fig. 5B illustrated 5-fold lower levels of K9.361 staining on GC B cells as compared with non-GC B cells. In Fig. 6, we presented the results of the semiquantitation of FcRIIB mRNA levels, via RT-PCR and in gel hybridization, in these two populations of B cells that had been purified by FACS. This figure indicated 6-fold lower levels of FcRIIB mRNA in GC, as compared with non-GC B cells.

In multiple recent experiments designed to extend these published studies, neither the reduced levels of K9.361 surface staining of B220⁺, IgD^–, GL7⁺ splenic B cells detected by flow cytometry or the reduced levels of FcRIIB mRNA in such cells isolated by FACS 8 days after i.p. immunization of C57BL/6 mice with SRBCs (evaluated via real-time RT-PCR) have been observed.

In several other figures in the above-referenced manuscript, the results of immunohistological analysis of FcRIIB expression in the GCs of SRBC immunized C57BL/6 mice were illustrated and interpreted to corroborate the results of the studies presented in Figs. 5 and 6. Due to the relative insensitivity of immunohistology as compared with flow cytometry, whether GC B cells stained 5- to 6-fold less intensely with anti-FcRIIB mAbs as compared with non-GC B cells could not have been unequivocally determined using the former approach. Nonetheless, our previous interpretations of these immunohistological data with regard to levels of FcRIIB on GC B cells appear to have been incorrect. In addition, arguments we forwarded in Discussion based on the conclusion that GC B cells express lower levels of FcRIIB than non-GC B cells may no longer hold merit.

We currently can provide no compelling explanation for why our previously published results on the expression levels of FcRIIB on GC B cells and the results of our more recent studies differ, but are actively investigating several possibilities. We should hasten to point out that our failure to reproduce the results presented in Figs. 5B and 6 does not influence the validity of any of the data or conclusions presented in the above-referenced manuscript regarding the expression and function of FcRIIB on follicular dendritic cells.

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