Production of antigen-specific human monoclonal antibodies: comparison of mice carrying IgH/kappa or IgH/kappa/lambda transloci.
Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise human mu chains that are associated with mouse lambda chains. In contrast, BABkappa,lambda mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa transloci) not only diminishes problems of endogenous mouse Iglambda expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.
Magadán
S
S
Universidad de Vigo, Pontevedra, Spain.
Valladares
M
M
Suarez
E
E
Sanjuán
I
I
Molina
A
A
Ayling
C
C
Davies
S L
SL
Zou
X
X
Williams
G T
GT
Neuberger
M S
MS
Brüggemann
M
M
Gambón
F
F
Diaz-Espada
F
F
González-Fernandez
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology / Q000502:physiology; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013045:Species Specificity; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains