Dynamics of Acquisition of Antigen and T Cell Help Influence B Cell Fate in the T-Dependent Humoral Immune Response

humoral immunity;Microbiology and Immunology;Health Sciences;Immunology

Turner, JacksonSwanson, Joel A ;

University of Michigan

关键词: humoral immunity;    Microbiology and Immunology;    Health Sciences;    Immunology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/140861/turnerjs_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The T-dependent humoral immune response is critical for generation of durable high-affinity antibody responses and protection from many pathogenic infections. B cell recruitment into the T-dependent humoral immune response requires acquisition of both antigen (Ag) and T cell help, and reacquisition of Ag and T cell help is thought to promote B cell proliferation, germinal center (GC) recruitment and selection, and differentiation into memory B cells and plasma cells (PCs). Despite the central role of Ag and T cell help in driving humoral immune responses, how the dynamics of acquisition of Ag and T cell help by B cells affect their participation in different stages of the T-dependent humoral immune responses is poorly understood. During the initial stages of the humoral immune response B cell access to Ag may be limited, and intravital imaging studies suggest that in some cases B cells;; early encounters with Ag may be transient. Whether B cells are tolerized or can be recruited into humoral immune responses following such encounters is not clear. We found that in contrast to B cells that continuously acquire Ag but not T cell help, B cells transiently exposed to Ag did not become anergic or undergo apoptosis in the absence of T cell help; rather they returned to a naïve-like state and were able to participate in subsequent immune responses. When T cell help was available, single transient Ag acquisition enabled B cell proliferation and differentiation into PCs and various subpopulations of memory B cells. Transient Ag acquisition also enabled B cells’ recruitment into GCs, even during the contraction phase of the GC response, in contrast to newly arriving B cells not preloaded with Ag, which were severely limited in their ability to participate in GCs after the peak of the GC response. Altogether these results indicate that when T cell help is available, transient Ag acquisition enables efficient recruitment of B cells into the T dependent humoral immune response, and favors B cell survival in the absence of T cell help.Within GCs, B cells compete for acquisition of Ag and T cell help following random mutation of their BCRs. Those that compete successfully are positively selected, and undergo further rounds of mutation and selection or differentiate into high-affinity PCs or memory B cells. The precise mechanisms of selection are still unclear and the individual roles of Ag acquisition and T cell help are an area of active investigation. While recent studies have provided evidence that competition for T cell help can drive selection of GC B cells, whether Ag acquisition can also support GC B cell selection independently of its role in promoting acquisition of T cell help is not known. We addressed the roles of Ag acquisition and T cell help separately and in combination and found that BCR cross-linking alone is not sufficient to promote GC B cell selection. Preliminary results suggest that BCR cross-linking is not necessary to promote T cell help based selection, but that it may enhance GC B cells;; expansion and differentiation into PCs.