Evidence for local expansion of IgA plasma cell precursors in human ileum.
IgA plays a crucial role in establishment and maintenance of mucosal homeostasis between host cells and commensal bacteria. To this end, numerous IgA plasma cells are located in the intestinal lamina propria. Whether the (immediate) precursor cells for these plasma cells can expand locally is not completely known and was studied here. The total number of IgA plasma cells in human ileal biopsies was counted. Sequence analysis of IgA V(H) genes from human ileal biopsies revealed the occurrence of many clonally related sequences within a biopsy, but not between different biopsies. This observation strongly argues for local expansion of IgA precursor cells. By comparing the number of unique sequences with the number of clonally related sequences within a biopsy, we estimated that approximately 100-300 precursors were responsible for the 75,000 IgA-producing cells that were present per biopsy. These precursor cells must therefore have divided locally 9-10 times. Since all sequences contained mutations and most of the mutations present in clonally related sequences were shared, the IgA precursor cells must have arrived initially as mutated cells in the lamina propria. Our data show evidence for the existence of two waves of expansion for IgA-producing cells in human ileum. The first wave occurs during initial stimulation in germinal centers as evidenced by somatic hypermutations. A second wave of expansion of IgA-committed cells occurs locally within the lamina propria as evidenced by the high frequency of clonally related cells.
Yuvaraj
Saravanan
S
Department of Cell Biology, Section Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Dijkstra
Gerard
G
Burgerhof
Johannes G M
JG
Dammers
Peter M
PM
Stoel
Maaike
M
Visser
Annie
A
Kroese
Frans G M
FG
Bos
Nicolaas A
NA
D001483:Base Sequence; D001706:Biopsy; D006801:Humans; D007082:Ileum / Q000276:immunology* / Q000378:metabolism; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D016415:Sequence Alignment; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology
D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region