Biased J<sub>H</sub> usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn’s disease

Dunn-Walters, Deborah K.; Boursier, Laurent; Hackett, Margaret; Spencer, Jo

doi:10.1136/gut.44.3.382

Cited by 10 publications

(10 citation statements)

References 27 publications

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“…Splenic Ig H genes sequenced in this study have the same characteristics as Ig H genes previously reported in other peripheral sites (13,16,21,24,25). It is also interesting to note that in this group of 32 splenic Ig genes there are two that use J H 1 segments, whereas no sequences from duodenum, salivary gland, or over 200 previously reported Ig genes from lamina propria plasma cells (10,11,17,19) were found that used J H 1. Because J H 1 is so rarely used anyway, a much larger sampling from spleen than this one would be required to determine whether this is significant.…”

Section: Discussionmentioning

confidence: 57%

“…Previous studies have indicated that the number of mutations in Ig H genes of gastrointestinal plasma cells is high (10,11,17,19) compared with published reports of the level of mutation in spleen, tonsil, and peripheral blood (16, 20 -25). However, we have shown that the number of mutations in IgA genes in lamina propria plasma cells of the duodenum is higher than the number in IgM genes (17).…”

Section: Discussionmentioning

confidence: 76%

“…IgA genes generally have higher numbers of mutations than IgG genes, which in turn have a higher number of mutations than IgM genes (16 -18). We have previously found, in humans, that B cells and plasma cells from the duodenum, ileum, and colon carry Ig H genes that have a much higher level of mutation (10,11,17,19). The reasons for the higher level of mutation are not yet known.…”

mentioning

confidence: 98%

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Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

Dunn‐Walters

Hackett

Boursier

et al. 2000

The Journal of Immunology

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Immunologically, the parotid salivary gland is an effector site that secretes large quantities of polyspecific Abs into the saliva, mainly of the IgA isotype. It is considered to be part of the common mucosal immune system but the inductive site for the Ab-producing cells of the salivary gland has not yet been clearly identified. The origin and diversity of cells of B lineage can be investigated by analyzing their Ig heavy chain genes (IgH). We have obtained sequences of IgM and IgA VH4–34 genes from plasma cells in human salivary gland, duodenal lamina propria, and splenic red pulp. Related sequences were found in different areas sampled within each tissue studied, indicating that the plasma cells carrying these genes are widespread with limited diversity. Examples of related IgH genes that are isotype switched were also seen in the salivary gland. The genes from plasma cells of the salivary gland were highly mutated, as were duodenal plasma cell sequences. The level of mutation was significantly higher than that seen in splenic plasma cell sequences. Analysis of CDR3 regions showed that the sequences from salivary gland had significantly smaller CDR3 regions than sequences from spleen, due to differences in number and type of DH regions used. Sequences from duodenum also had smaller CDR3 regions. Therefore, plasma cells from human duodenum and salivary gland showed characteristics that differed from those of human splenic plasma cells.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 98%

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Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

Dunn‐Walters

Hackett

Boursier

et al. 2000

The Journal of Immunology

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“…20 This finding is consistent with studies on B-cell receptor gene usage that have demonstrated that infiltrating lymphocytes in UC mucosa are of peripheral rather than mucosal origin. 21,22 IgG1 and IgG4 antibodies predominate in UC, whereas IgG2 antibodies are increased in CD. 23 The prevalence of the IgG1 type has recently been explored and shown to be specific to UC and lead to greater opsonization of mucosal bacteria and a feed-forward maintenance of the polymorphonuclear leukocyte respiratory burst in UC.…”

Section: Discussionmentioning

confidence: 99%

Molecular Classification of Crohn's Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells

Burczynski¹,

Peterson²,

Twine³

et al. 2006

The Journal of Molecular Diagnostics

219

159

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Ulcerative colitis (UC) and Crohn's disease (CD) are common inflammatory bowel diseases producing intestinal inflammation and tissue damage. Although emerging evidence suggests these diseases are distinct, ϳ10% of patients remain classified as indeterminate inflammatory bowel disease even after invasive colonoscopy intended for diagnosis. A molecular diagnostic assay using a clinically accessible tissue would greatly assist in the classification of these diseases. In the present study we assessed transcriptional profiles in peripheral blood mononuclear cells from 42 healthy individuals, 59 CD patients, and 26 UC patients by hybridization to microarrays interrogating more than 22,000 sequences. Supervised analysis identified a set of 12 genes that distinguished UC and CD patient samples with high accuracy. The alterations in transcript levels observed by microarray were verified by real-time polymerase chain reaction. The results suggest that a peripheral blood mononuclear cell-based gene expression signature can provide a molecular biomarker that can complement the standard diagnosis of UC and CD.

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“…Three of the nine patients were women and the group had an mean age of 59 years (range 49-90). Mean duration of disease was 8.4 years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Biopsies were taken from the anterior rectal wall, 5-10 cm from the anal verge.…”

Section: Patients and Controlsmentioning

confidence: 99%

Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response

Furrie

Macfarlane²,

Macfarlane³

2004

Gut

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Background and aims: The mucosa in ulcerative colitis (UC) is replete with antibody producing plasma B cells and polymorphonuclear leucocytes (PMN). This combination of effector cells requires a crosslinking antigen to evoke an antibody driven PMN inflammatory response via their Fc receptors. The stimulus for activation is thought to be commensal bacteria colonising the gut mucosa. The aim of this investigation was to compare the principal culturable bacterial populations on the rectal mucosa of UC patients, and to determine whether specific antibodies towards these bacteria can activate infiltrating PMN through opsonisation. This would provide an explanation for this chronic inflammatory condition. Methods: Bacteria colonising rectal tissue were characterised using chemotaxonomic techniques. Systemic antibody responses were measured against total antigens and surface antigens of these organisms in UC and Crohn's disease (CD) patients, together with healthy controls. Antibody enhancement of the respiratory burst in PMN was also investigated, against a range of mucosal isolates. Results: Distinct differences were observed in some bacterial populations in UC biopsies, which were generally reflected in antibody responses towards these organisms. UC patients had higher IgG responses to surface antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies from UC patients greatly enhanced the respiratory burst in PMN, in response to individual bacterial species. Conclusions: Changes in mucosal bacteria, and a switch from internal to surface antigen/antibody reactivity of a predominantly IgG1 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC.

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Biased J_H usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn’s disease

Cited by 10 publications

References 27 publications

Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

Molecular Classification of Crohn's Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells

Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response

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Biased JH usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn’s disease

Cited by 10 publications

References 27 publications

Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

Characteristics of Human IgA and IgM Genes Used by Plasma Cells in the Salivary Gland Resemble Those Used in Duodenum But Not Those Used in the Spleen

Molecular Classification of Crohn's Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells

Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response

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Biased J_H usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn’s disease