title: Is there a typical germinal center? A large-scale immunohistological study on the cellular composition of germinal centers during the hapten-carrier-driven primary immune response in mice.
abstract: Germinal centers (GCs) are complex, multicell-type, transient structures that form in secondary lymphatic tissues in response to T cell-dependent stimulation. This process is crucial to the adaptive immune response because it is the source of affinity maturation and long-lived B cell memory. Our previous studies showed that the growth of murine splenic GCs is nonsynchronized, involving broad-volume distributions of individual GCs at any time. This raises the question whether such a thing as a typical GC exists. To address this matter, we acquired large-scale confocal data on GCs throughout the course of the 2-phenyl-5-oxazolone chicken serum albumin-driven primary immune response in BALB/c mice. Semiautomated image analysis of 3457 GC sections revealed that, although there is no typical GC in terms of size, GCs have a typical cellular composition in that the cell ratios of resident T cells, macrophages, proliferating cells, and apoptotic nuclei are maintained during the established phase of the response. Moreover, our data provide evidence that the dark zone (DZ) and light zone (LZ) compartments of GCs are about the same size and led us to estimate that the minimal cell loss rate in GCs is 3% per hour. Furthermore, we found that the population of GC macrophages is larger and more heterogeneous than previously thought, and that despite enrichment of T cells in the LZ, the DZ of murine splenic GCs is not poor in T cells. DZ and LZ differ in the T cell-to-macrophage ratio rather than in the density of T cells.
authors.affiliation: Systems Immunology Laboratory, Department of Biology, Humboldt University Berlin, D-10115 Berlin, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wittenbrink
authors.forename: Anke
authors.initials: A
authors.lastname: Klein
authors.forename: Armin A
authors.initials: AA
authors.lastname: Weiser
authors.forename: Johannes
authors.initials: J
authors.lastname: Schuchhardt
authors.forename: Michal
authors.initials: M
authors.lastname: Or-Guil
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000276:immunology*; D002451:Cell Compartmentation / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells; D003430:Cross-Sectional Studies; D005455:Fluorescent Antibody Technique; D018858:Germinal Center / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D006241:Haptens / Q000008:administration & dosage* / Q000276:immunology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010081:Oxazolone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D012709:Serum Albumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D006241:Haptens; D012709:Serum Albumin; C018361:2-phenyloxazolone; D010081:Oxazolone