IgVH gene analysis suggests that peritoneal B cells do not contribute to the gut immune system in man.
The contribution of peritoneal B cells to the intestinal lamina propria plasma cell population is well documented in mice, but unknown in humans. We have analyzed immunoglobulin (Ig) genes of human peritoneal B cells, because such genes show distinctive characteristics in mucosal B cells, particularly highly mutated variable regions. Here, we report the characteristics of variable region genes used by IgM, IgA and IgG in peritoneal cells. We focused on the properties of IgV(H)4-34 to allow comparisons of like-with-like between different isotypes and cells from different immune compartments. We observed that the IgM genes were mostly unmutated, and that the mutated subset had less mutations than would be expected in a mucosal B cell population. Likewise, the IgV(H)4-34 genes used by IgA and IgG from peritoneal B cells had significantly lower numbers of mutations than observed in the mucosal counterparts. Other trends observed, while not reaching statistical significance, followed the trend of peripheral B cells. The peritoneal B cell population had more IgA1 than IgA2 sequences, and there was no dominance of J(H)4 in the IgA from peritoneum or spleen, in contrast to the mucosal sequences. Overall, this study suggested that human peritoneal B cell are either peripheral or mixed in origin; they are unlikely to represent an inductive compartment for the mucosal B cell system.
Guy's, King's and St Thomas' Medical School, Department of Histopathology, St Thomas' Campus, London, GB.
Laurent
L
Boursier
Inger Nina
IN
Farstad
Jan Roar
JR
Mellembakken
Per
P
Brandtzaeg
Jo
J
Spencer
D000293:Adolescent; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D022801:Complementarity Determining Regions / Q000235:genetics; D004386:Duodenum / Q000166:cytology / Q000276:immunology; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D027041:Somatic Hypermutation, Immunoglobulin; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology
D022801:Complementarity Determining Regions; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region