The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response.
The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE(+) cells in memory responses is particularly unclear. IgE(+) B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE(+) GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE(+) GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE(+) GC cells, whereas sequential switching gives rise to IgE(+) PCs. We propose a comprehensive model for the generation and memory of IgE responses.
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648.
Jin-Shu
JS
He
Michael
M
Meyer-Hermann
Deng
D
Xiangying
Lim Yok
LY
Zuan
Leigh Ann
LA
Jones
Lakshmi
L
Ramakrishna
Victor C
VC
de Vries
Jayashree
J
Dolpady
Hoi
H
Aina
Sabrina
S
Joseph
Sriram
S
Narayanan
Sharrada
S
Subramaniam
Manoj
M
Puthia
Glenn
G
Wong
Huizhong
H
Xiong
Michael
M
Poidinger
Joseph F
JF
Urban
Juan J
JJ
Lafaille
Maria A
MA
Curotto de Lafaille
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018448:Models, Immunological; D009559:Nippostrongylus; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology
D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D049452:Green Fluorescent Proteins; D007073:Immunoglobulin E