Disease relevance of Igj

• The B cell lymphoma WEHI-231 does not express J chain, and the majority of its secreted IgM is polymerized as hexamers [1].
• Following HSV-2 genital infection, the Jch(-/-) mice consistently exhibited fewer vaginal symptoms (P = 0.010) and mortality (P = 0.075) than did the WT mice [2].
• Decreased vaginal disease in J-chain-deficient mice following herpes simplex type 2 genital infection [2].
• J-chain-deficient (Jch(-/-)) mice were used to study the role of polymeric IgA (pIgA) in primary disease and protective immunity following genital herpes simplex type 2 (HSV-2) infection [2].
• Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in fully immunocompetent, T cell-depleted, beta2-microglobulin-deficient, and J chain-deficient mice [3].

High impact information on Igj

• The observation that J chain may be constitutively expressed in human B cells and the possibility that J chain performs additional regulatory functions in monomer-Ig secreting cells should be pursued [4].
• Analyses of the expression of J chain mRNA and protein in mouse lymphocytes have shown that the initiation and amplification of J-chain synthesis are critical steps in the pentamer IgM response because the J polypeptide is required for the assembly of the IgM antibody [4].
• A model system for peptide hormone action in differentiation: interleukin 2 induces a B lymphoma to transcribe the J chain gene [5].
• Expression of J chain RNA in cell lines representing different stages of B lymphocyte differentiation [6].
• No J chain-specific RNA could be demonstrated in a lymphoma line representative of an undifferentiated B lymphocyte, but three species of J chain RNA were identified in hybrid cell lines representative of IgM-secreting plasma cells: a mature message of approximately 1.5 kb and two minor components of 2.5 and 0.92 kb [6].

Chemical compound and disease context of Igj

• We report here that the regulatory mechanisms which lead to increased levels of MMTV transcripts in differentiating, lipopolysaccharide (LPS)-stimulated normal B cells and in the inducible B-cell lymphoma line CH12 are at least partially distinct from those controlling increases in immunoglobulin and J-chain gene expression [7].

Biological context of Igj

• Analysis of single B cells stimulated by lipopolysaccharide in vitro using reverse transcription-polymerase chain reaction showed that J chain-nonexpressing B cells could be detected that had a secretory phenotype as determined by an abundance of transcript for secretory IgM [8].
• We conclude that although the J chain is not required for IgA dimerization, it does affect the efficiency of polymerization or have a role in maintaining IgA dimer stability [9].
• Restriction mapping experiments further suggested the existence of a single J chain gene per haploid genome [10].
• The amino acid sequence deduced for the mature mouse J chain was found to be 74% identical with that previously determined for the human J chain [11].
• Analysis of the coding regions showed that the J chain gene has a different structure from the other immunoglobulin genes [12].

Anatomical context of Igj

• Finally, limiting dilution analysis of peripheral B cells showed that J chain expression was a clonal property already established in naive, peripheral B lymphocytes [8].
• In addition, immunohistochemistry showed J-chain-positive plasma cells in the intestine and spleen [13].
• These results suggest the presence of a mucosal immune system mainly composed of J-chain-containing Ig in the turtle [13].
• Thus, CH12.LX cells provide a model cell line in which the role of the IL-2R beta chain in differentiative events such as J chain upregulation can be examined [14].
• Oligomeric, J-chain-containing immunoglobulins were observed to be transferred selectively from serum into colostrum [15].

Associations of Igj with chemical compounds

• The conventional model of polymeric IgM depicts a unique structure in which the mu heavy chains and J chain are joined by well defined disulfide bonds involving cysteine residues at positions 337, 414 and 575 of the mu chain [16].
• However, comparison of 5-methylcytosine contents showed that J chain gene expression correlates with a loss of methyl groups [17].
• The primary encounter of a B cell with antigen must therefore trigger events that effect J chain gene transcription through a mechanism involving loss of methyl groups from cytosine [17].
• Also, we found that the glycosylation site at asparagine 563 of mu tp was important for J chain incorporation [18].
• Disruption of this site by replacement of either asparagine 563 by tyrosine or serine 565 by phenylalanine resulted in diminished J chain incorporation and increased production of hexameric IgM [18].

Physical interactions of Igj

• Interleukin 2- and interleukin 5-induced changes in the binding of regulatory factors to the J-chain gene promoter [19].

Regulatory relationships of Igj

• Both IL-5 and IL-6 can independently stimulate increases in steady-state levels of immunoglobulin and J-chain mRNA and proteins, and they both induce the differentiation of CH12 into high-rate antibody-secreting cells [20].
• A major interleukin 2 (IL-2)-responsive region that contains two adjacent control elements (JA and JB) exists within the J chain promoter [21].
• Transcription factor PU.1 positively regulates J chain gene expression by binding to one of the control elements (JB) in the J chain promoter [21].
• Interleukin 5 stimulated higher production of J chain RNA and protein than LPS, while LPS induced the highest levels of the secretory form of mu protein [22].

Other interactions of Igj

• Expression of the immunoglobulin J chain in a murine B lymphoma is driven by autocrine production of interleukin 2 [14].
• Expression of the Ig J chain and the secreted form of Ig mu, which are both known to be suppressed by Pax-5a in mature B cells, were increased in B cells of aged mice [23].
• When the immunoglobulin-producing myeloma MPC11 is fused to a T lymphoma, Oct-2 production ceases, as does the expression of immunoglobulin, J chain, and several other B cell-specific gene products [24].
• However, the presence of anti-CD27 significantly inhibits the induction of Blimp-1 and J chain transcripts, which are turned on in cells committed to plasma cell differentiation [25].
• The major findings were: 1) J chain can be found in an IgG2b-secreting cells (MPC-11) [26].

Analytical, diagnostic and therapeutic context of Igj

• The primary structure of the murine J chain was investigated by sequence analysis of the J chain cDNA inserts from two independently cloned chimeric plasmids [11].
• Northern blot analysis revealed that turtle J-chain mRNA was expressed in lung, stomach, spleen and intestine [13].
• Western blot analysis was carried out in order to compare the protein levels of J and mu heavy chains in serum from day 8 to day 24 after birth, using antihuman J chain and antimouse mu chain antibodies [27].
• The expression of functional J chain mRNA was evaluated by cell-free translation and specific immunoprecipitation of a J chain product [6].
• The expression of precursor mRNA was examined by hybridization with a J chain probe obtained by molecular cloning of cDNA [6].

References