Biomaterial Database

In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. 2001

S Fagarasan, and K Kinoshita, and M Muramatsu, and K Ikuta, and T Honjo

Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

One of the front lines of the immune defence is the gut mucosa, where immunoglobulin- (IgA) is continuously produced to react with commensal bacteria and dietary antigens. It is generally accepted that, after antigenic stimulation in the Peyer's patches, IgA+ lymphoblasts (B220+IgA+) migrate through the lymph and blood circulation, and eventually home to the lamina propria of the intestine. Mice that lack activation-induced cytidine deaminase (AID) are defective in class switch recombination (CSR) and somatic hypermutation. CSR changes the immunoglobulin heavy chain constant region (CH) gene being expressed from Cmu to other CH genes, resulting in a switch of the immunoglobulin isotype from IgM to IgG, IgE or IgA. AID-/- mice also secrete large amounts of immunoglobulin-mu (IgM) into faeces, and accumulate B220-IgM+ plasma cells as well as B220+IgM+ cells in the gut. Here we show that lamina propria B220+IgA+ cells have just completed CSR, as they still express both AID and transcripts from circular DNA that has been 'looped-out' during CSR. Lamina propria IgM+ B cells seem to be pre-committed to switching to IgA+ in vitro as well as in vivo. Culturing lamina propria IgM+ B cells together with lamina propria stromal cells enhances preferential switching and differentiation of B cells to IgA+ plasma cells. We conclude that IgA+ cells in the gut lamina propria are generated in situ from B220+IgM+ lymphocytes.

UI	MeSH Term	Description	Entries
D007070	Immunoglobulin A	Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.	IgA,IgA Antibody,IgA1,IgA2,Antibody, IgA
D007075	Immunoglobulin M	A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin.	Gamma Globulin, 19S,IgM,IgM Antibody,IgM1,IgM2,19S Gamma Globulin,Antibody, IgM
D007413	Intestinal Mucosa	Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.	Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008808	Mice, Inbred CBA	An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH.	Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010581	Peyer's Patches	Lymphoid tissue on the mucosa of the small intestine.	Patches, Peyer's,Peyer Patches,Peyers Patches
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003564	Cytidine Deaminase	An enzyme that catalyzes the deamination of cytidine, forming uridine. EC 3.5.4.5.	Cytidine Aminohydrolase,Aminohydrolase, Cytidine,Deaminase, Cytidine
D004270	DNA, Circular	Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)	Circular DNA,Circular DNAs,DNAs, Circular
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia