Humoral immune functions in IL-4 transgenic mice.
We have analyzed mice expressing IL-4 as a transgene, and found that expression of this lymphokine has profound effects on B cell function. B cells from transgenic mice exhibit phenotypic changes, including an increase in size and elevated expression of class II MHC. IL-4 increases the quantity of IgE produced by transgenic-derived B cells in response to LPS stimulation. In vivo, IL-4 markedly affects the serum Ig isotype repertoire. Serum levels of IgG1 and IgE are elevated, and levels of IgG2a, IgG2b, and IgG3 are depressed in IL-4 transgenic mice. Ag-specific antibody responses to immunization with hapten-carrier conjugates are also affected by IL-4. Transgenic mice show increased anti-hapten IgE and IgG1 and reduced anti-hapten IgG2a, IgG2b, and IgG3, compared with wild-type mice. Ag-specific IgE is substantially induced by T cell-dependent Ag, but not T cell-independent Ag, suggesting that cognate T-B interactions in addition to IL-4 are required for generating IgE responses in vivo. In vivo treatment with the anti-IL-4 mAb 11B11 reverses many of the isotype alterations in the transgenic mice, indicating that these changes arise as a direct consequence of IL-4 secretion.
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
H J
HJ
Burstein
R I
RI
Tepper
P
P
Leder
A K
AK
Abbas
D000818:Animals; D000917:Antibody Formation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D005434:Flow Cytometry; D015847:Interleukin-4 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000955:Antigens, T-Independent; D014301:Trinitrobenzenes; D015847:Interleukin-4