Soluble CD14 enriched in colostrum and milk induces B cell growth and differentiation.
Induction of resting B cell growth and differentiation requires a complex series of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each rendering the B cell susceptible to factors supporting progressive activation. Here, we demonstrate that soluble CD14 (sCD14) bypasses the physiological sequelae of events that limit B cell activation. B cell growth and differentiation in vitro is induced by both native and recombinant forms of sCD14 at nanomolar concentrations. sCD14-mediated cellular activation does not require membrane CD14 expression, depends on a region of CD14 that is not involved in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administration to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin.
Filipp
D
D
Department of Immunology, University of Toronto, and The Arthritis and Immune Disorder Research Centre, The Toronto Hospital, Toronto, ON, Canada M5G 2M9.
Alizadeh-Khiavi
K
K
Richardson
C
C
Palma
A
A
Paredes
N
N
Takeuchi
O
O
Akira
S
S
Julius
M
M
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D003126:Colostrum / Q000737:chemistry*; D003433:Crosses, Genetic; D016895:Culture Media, Serum-Free; D029721:Drosophila Proteins; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008895:Milk, Human / Q000737:chemistry*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D012995:Solubility; D013154:Spleen / Q000166:cytology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000911:Antibodies, Monoclonal; D016895:Culture Media, Serum-Free; D029721:Drosophila Proteins; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors