Extraction and intracellular trafficking of membrane associated antigen distinguishes human germinal center B cells from naïve B cells and memory B cells

Autor: Kihyuck Kwak, Avva Saniee, Nicolas Quizon, Haewon Sohn, Susan Pierce
Rok vydání: 2018
Předmět:
Zdroj: The Journal of Immunology. 200:99.25-99.25
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.200.supp.99.25
Popis: Protective antibody responses to vaccination or infection in humans depend on the competitive selection of high-affinity germinal-center (GC) B cells into the long-lived memory B cell compartment. Selection is determined in large part by the ability of GC B cells to gather, process and present antigen to T follicular helper T cells (TFH cells). We have shown that human GC B cells are better able to distinguish their affinity for antigen as compared to naïve B cells in the gathering and internalization of antigen. Here we provide evidence that human naïve B cells and GC B cells rely on different endocytic processes for antigen internalization and trafficking. We found that the Microtubule Organizing Centers in activated GC B cells were not polarized toward the immune synapse with the antigen-containing membrane as in naïve B cells but rather dispersed large distances from the immune synapse in GC B cells. GC B cells trafficked antigen-bound BCRs from the synapse outside the sides of the cells to distal sites for internalization whereas naïve B cells internalized antigen from the immune synapse. Moreover, as compared to naïve B cells, LAMP-1+ vesicles in GC B cells were less polarized and less internalized antigen was colocalized with LAMP-1+ vesicles. We also found that the expression of SNX9 and SNX18, key components of the endocytosis machinery and modulators of clathrine mediated endocytosis, was significantly lower in GC B cells as compared to naïve B cells and SNX9 and SNX18 were poorly polarized toward the immune synapse in activated GC B cells. We propose that these differences in endocytosis processes for antigen internalization contribute the higher affinity thresholds of GC B cells.
Databáze: OpenAIRE
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