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Jo Spencer Biography

Professor in Experimental Medicine

Head of the Department of Immunobiology

King’s College London Medical School

Guy’s Hospital.

Our laboratory is currently studying autoimmune diseases and their association with mucosal surfaces such as the nasal mucosal and gut.

Wegener’s granulomatosis (GPA or Granulomatosis with polyangiitis) is of particular interest to us because there is evidence that in many cases the autoimmune vasculitis is preceded by a prolonged chronic inflammatory phase in the nasal mucosa and airways.  We are currently collaborating closely with Professor David D’Cruz and his Clinical team at the Louise Coote Lupus unit to investigate the evolution of GPA; from localized inflammation to systemic vasculitis.

Our laboratory has an established track record studying human cells and tissues and successful collaborations with clinical teams.

-The first characterisation of gut associated lymphoid tissue in human appendix and Peyer’s patches, and identification of B cell subsets and their relationship to B cell lymphoma of mucosa-associated lymphoid tissue.

-First description of the gamma delta T cells in human intestinal epithelium and the expansion of this subset of T cells in celiac disease (1). Other T cell subsets were also described for the first time.

-Definition of a causal relationship between T cell activation and epithelial cell proliferation in the intestine (2). This study is relevant to pathologies with crypt cell hyperplasia including celiac disease and ulcerative colitis.

-First description of antibody autoreactivity in B cell lymphoma of mucosa associated lymphoid tissue, then identification of a causal relationship between infection of the gastric mucosa with Helicobacter pylori and tumour progression (3). This study underpinned a sister paper describing the regression of lymphoma following antibiotic treatment, by providing a scientific rationale. These studies revolutionized treatment of this particular type of gastric malignancy.

-First definition of the human marginal zone as a memory B cell compartment (4) defining a relationship between histology and function.

-The dynamic characteristics of human gut associated lymphoid tissue have been defined  by combining histology with study of B cell/ plasma cell clonal evolution using immunoglobulin gene analysis. We conclude that human intestinal plasma cells originate from the organized lymphoid tissue in the gut and disseminate widely through the intestine (5, 6). These studies have had a major contribution to understanding of human mucosal antibody responses.

-Immunoglobulin genes used by intestinal plasma cells are highly mutated by somatic hypermutation. Analysis of the microsequence preferences associated with mutations in these sequences allowed us to define that GC and AT nucleotides are targeted by different mutators (7), before the discovery of activation induced cytidine deaminase, now known the be the GC mutator.

-First description of immunoglobulin light chain revision in the gut (8).  Light chain revision is capable of modifying the immunoglobulin repertoire (9), a finding that is of fundamental importance to our understanding of the stability of the antibody response generally.

-Identification of local allergic component in the disease orofacial granulomatosis.  This collaboration with gastroenterologists and oral pathologists has provided a scientific basic for clinical observations, and has supported changes in patient management (10).

Scientific references supporting the statements above.

1. Spencer J and Isaacson PG (1989). Human T-cell receptor expression. Nature. 337: 416.

2. MacDonald TT and Spencer J (1988). Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J. Exp. Med. 167: 1341-1349.

3. Hussell T, Isaacson PG, Crabtree JE and Spencer J (1993). The response of cells from low grade B cell gastric lymphomas of mucosa associated lymphoid tissue to Helicobacter pylori. Lancet 342: 571-574.

4. Dunn-Walters DK, Isaacson PG and Spencer J (1995). Analysis of mutations in IgVH genes of microdissected marginal zone B cells suggests that the marginal zone of human spleen is a reservoir of memory B cells. J Exp Med 182: 559-566.

5. Boursier L, Gordon JN, Thiagamoorthy S, Edgeworth JD and Spencer J (2005). Human intestinal IgA response is generated in the organized gut-associated lymphoid tissue but not in the lamina propria. Gastroenterology 128, 1879-1889.

6. Barone F, Patel P, Sanderson JD and Spencer J. (2009) Gut-associated lymphoid tissue contains the molecular machinery to support T-cell-dependent and T-cell-independent class switch recombination. Mucosal Immunol. 2:495-503

7. Spencer J, Dunn M and Dunn-Walters DK (1999) Characteristics of sequences around individual nucleotide substitutions in IgVH genes suggest different GC and AT mutators. J. Immunol. 162: 6596-6601

8. Su W, Boursier L, Padala A, Sanderson JD and Spencer J (2004). Biases in immunoglobulin lambda light chain rearrangements in human intestinal plasma cells. J Immunol 172, 2360-2366.

9. Su W, Gordon JN, Barone F, Boursier L, Turnbull W, Mendis S, Dunn-Walters DK, and Spencer J. (2008) Lambda light chain revision in the human intestinal IgA response. J Immunol 181: 1264-1271.

10. Patel P, Barone F, Nunes C, Boursier L, Odell E, Escudier M, Challacombe S, Brostoff J, Spencer J, Sanderson J. (2009) Subepithelial dendritic B cells in orofacial granulomatosis. Inflamm Bowel Dis. 2009 Nov 18. [Epub ahead of print]

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