FcgRII-I is an inhibitory receptor expressed in both naive and memory B cells. However, in naive B cells, this receptor prevent the response against antigens for which there are preformed antibodies while this is not the case in memory B cells. Is there any known mechanism by which FcgRIIB-I inhibits naive B cells but not memory B cells?
Perhaps this may help?
Intrinsic Differences in the Initiation of B Cell Receptor Signaling Favor Responses of Human IgG+ Memory B Cells over IgM+ Naive B Cells
Angel M. Davey and Susan K. Pierce
The acquisition of long-lived memory B cells (MBCs) is critical for the defense against many infectious diseases. Despite their im- portance, little is known about how Ags trigger human MBCs, even though our understanding of the molecular basis of Ag ac- tivation of B cells in model systems has advanced considerably. In this study, we use quantitative, high-resolution, live-cell imaging at the single-cell and single-molecule levels to describe the earliest Ag-driven events in human isotype-switched, IgG-expressing MBCs and compare them with those in IgM-expressing naive B cells. We show that human MBCs are more robust than naive B cells at each step in the initiation of BCR signaling, including interrogation of Ag-containing membranes, formation of submicroscopic BCR oligomers, and recruitment and activation of signaling-associated kinases. Despite their robust response to Ag, MBCs remain highly sensitive to FcgRIIB-mediated inhibition. We also demonstrate that in the absence of Ag, a portion of MBC receptors sponta- neously oligomerized, and phosphorylated kinases accumulated at the membrane and speculate that heightened constitutive signaling may play a role in maintaining MBC longevity. Using high-resolution imaging, we have provided a description of the earliest events in the Ag activation of MBCs and evidence for acquired cell-intrinsic differences in the initiation of BCR signaling in human naive and MBCs. The Journal of Immunology, 2012, 188: 000–000.
I don't know off hand, but a guess is that wiring around SHIP and CD22 could be different in naive and memory B cells. We could not confirm the study suggesting using very manipulated mouse B cell lines that CD22 doesn't associate with the IgG BCR (Wakabayashi C, Adachi T, Wienands J, Tsubata T. Science. 2002. 298:2392-5), but nevertheless, CD22 is worth considering in some context. Great question!
Thanks for replying to my question. Dr. Burlak, great work thanks for sharing it. When I teach this topic, I tell my students two possible explanations: A) memory B cells display Ig with greater affinity for the antigen -they have undergone affinity maturation- than naive B cells, which might also be expressed at higher levels and B) The inhibitory FcR might be expressed at greater levels in naive B cells than memory B cells. I wonder if someone has checked. Dr. Clark´s guess is also a good explanation.
Getting back to this issue I have found a very interesting manuscript showing that the expression of the inhibitory FcgRIIB-I receptor is downregulated in the germinal centers. Here goes a link to the article: http://www.ncbi.nlm.nih.gov/pubmed/12165510.
This article provides insights onto B cell memory development and it would support that memory B cells, unlike naive B cells, can respond to antigens in the presence of preformed antigen-specific antibodies due to downregulation of the inhibitory receptor FcgRIIB-I.
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