Surrogate or conventional light chains are required for membrane immunoglobulin mu to activate the precursor B cell transition.
To examine the role of light chains in early B cell development we combined RAG-1 and lambda 5 mutations to produce mice that expressed neither conventional nor surrogate light chains (RAG-1-/-, lambda 5-/-). Unique heavy and light chain genes were then introduced into the double and single mutant backgrounds. Membrane immunoglobulin (Ig)mu (mIg mu) associated with Ig alpha-Ig beta but was unable to activate the pre-B cell transition in RAG-1-/-lambda 5-/- mice. Either lambda 5 or kappa light chains were sufficient to complement this deficiency. Therefore light chains are absolutely required for a functional Ig signaling module in early B cell development. Our data provide direct evidence for the existence of two pathways for induction of early B cell development: one which is activated through surrogate light chains and mIg mu, and an alternative pathway which uses conventional light chains and mIg mu.
Papavasiliou
F
F
Laboratory of Molecular Immunology, Howard Hughes Medical Institute, Rockefeller University, New York 10021, USA.
Jankovic
M
M
Nussenzweig
M C
MC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002472:Cell Transformation, Viral; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell