Murine heavy chain disease

Abstract

Using cultured mouse myeloma cells, it has been possible to derive cells which are now synthesizing products similar to human heavy chain disease proteins. An initial mutant was isolated which snythesized a heavy chain with an internal deletion and a normal light chain. In a subsequent step, a variant was identified in which the synthesis of the heavy chain with the deletion persisted in the absence of light chain synthesis. These experiments also demonstrate that in the MPC-11-derived cultured cell line, the continued synthesis of heavy chain does not require the synthesis of light chain.

Expression of a Dromedary Heavy Chain-Only Antibody and B Cell Development in the Mouse

“…H chains with the long hydrophobic transmembrane region anchor in the lipid bilayer, whereas the short hydrophilic C-terminal region of secretory form H chains ensures their release from the cell in the absence of associated BiP. The importance of the C H 1 domain is well recognized because hybridoma or myeloma cell lines harboring Ig genes with deleted C H 1 exon retain the ability to secrete homodimeric H chains without associated L chains (46,47). In heavy chain disease, truncated H chains are readily secreted without L chain (17,48).…”

Two alpha heavy chain disease proteins with different genomic deletions demonstrate that nonexpressed alpha heavy chain genes contain methylated bases.

“…Many different deletion mutants of.heavy chains have been described (10)(11)(12)(25)(26)(27)(28)(29). One y H chain mutant, IF2, with an internal deletion of the entire CH1 domain (27,30) (Fig.…”

“…In man, the steps that lead to the production ofdeleted H chains are not precisely defined; however, in the murine example, the H chain disease arose in two steps: first, a deleted H (AH) and a normal L chain were synthesized, and then a secondary variant synthesizing only AH was identified (12). The mechanism for the generation of the deletion in the H chain remains obscure.…”

Molecular basis of the cell-surface expression of immunoglobulin mu chain without light chain in human B lymphocytes.

“…A 19-mer synthetic oligonucleotide complementary to nucleotides [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] (CAl. 1) and an 18-mer synthetic oligonucleotide complementary to nucleotides 26-44 (CL1.3) of the human CIL1 exon (22) were used as primers to initiate cDNA synthesis (see Fig.…”

“…Certain instances can arise though where more mature B-lymphoid cells can also stably express H chains in the absence of any light (L)-chain synthesis. The best documented examples of this phenomenon are found in plasma cell stage lines isolated from patients with 'y H-chain disease (4) or represented by certain variant clones isolated during culture of mouse plasmacytomas (5). The H chain produced by the plasmacytoid cell lines from each of these sources is always found to be structurally altered from the native H-chain protein of the same isotype and is generally secreted by the cell as an H-chain-only multimeric complex.…”