IgE+ memory B cells and plasma cells generated through a germinal-center pathway

Abstract

Immunoglobulin E (IgE) antibodies are pathogenic in asthma and allergic diseases, but the in vivo biology of IgE-producing (IgE(+)) cells is poorly understood. A model of the differentiation of IgE(+) B cells proposes that IgE(+) cells develop through a germinal-center IgG1(+) intermediate and that IgE memory resides in the compartment of IgG1(+) memory B cells. Here we have used a reporter mouse expressing green fluorescent protein associated with membrane IgE transcripts (IgE-GFP) to assess in vivo IgE responses. In contrast to the IgG1-centered model of IgE switching and memory, we found that IgE(+) cells developed through a germinal-center IgE(+) intermediate to form IgE(+) memory B cells and plasma cells. Our studies delineate a new model for the in vivo biology of IgE switching and memory.

Control of the STAT6–BCL6 Antagonism by SWAP-70 Determines IgE Production

“…These modes must not be mutually exclusive, and their usage may depend on various parameters such as the route of stimulation or whether low or high affinity IgE is produced. This is illustrated, for example, by the absence of sequential switching upon anti-IgD injection into mice or in the N. strongylus-induced direct switch to IgE (26,49). The efficient formation of highaffinity IgE requires an IgG1 intermediate, and IgG1 patterns of somatic hypermutation can be transferred to IgE molecules (51).…”

Enhanced cell‐binding by allergen multimers: how complex is it?

“…In particular, two groups independently invested in the generation of IgE reporter mice to address the vexing question of the route of development of the elusive IgE þ B cell. 2,3 Two new anti-IgE mAb targeting membrane IgE and cell-bound IgE have the potential to deplete the cellular source of IgE. 4,5 These could be candidates for alternative anti-IgE treatment options with advantages over current anti-IgE therapy (OmalizumAb), which depletes free serum IgE.…”

“…Although controversial, memory T cells may also be intrinsically augmented in their proliferative response to antigen relative to naïve T cells. 3,4 In addition, memory cells possess the ability to maintain their numbers through homeostatic turnover in response to the cytokine interleukin (IL)-15. Overall, these findings reinforce the view that memory T cells are in a fundamentally different proliferative state to naïve and effector T cells.…”

Addendum: IgE+ memory B cells and plasma cells generated through a germinal-center pathway

“…We were concerned that in our previous study we may not have clearly separated IgG1 + and IgE + B cells in our studies of IgE memory, which used the fluorescence intensity of GFP to separate IgG1 + and IgE + memory B cell populations for adoptive transfer 1 (Fig. 1b), we calculate that the IgG1 + GFP hi memory B cells contributed approximately 25% of the total serum IgE response in one study (Fig.…”

“…It has come to our attention that in our studies of the differentiation and memory of IgE + B cells in mice, we did not appropriately distinguish IgG1 + and IgE + B cells because of technical flaws in our original flow cytometry 1,2 . After changing the fluorochrome of the antibody to IgG1 from phycoerythrin to allophycocyanin to overcome problems in the compensation between the green fluorescent protein (GFP) and IgG1 channels of our original nine-color analysis of in vivo IgG1 + and IgE + B cell populations, we identified the following three distinct IgG1 + and IgE + B cell populations in our IgE-GFP reporter mice infected with Nippostrongylus brasiliensis: IgG1 + GFP -IgG1-expressing cells, IgG1 + GFP hi IgG1-expressing cells and IgG1 -GFP hi IgE-expressing cells (Fig.…”