Requirements for the adoptive transfer of antibody responses to a priming antigen in man.
Antibody responses to recall vaccines can be adoptively transferred after marrow transplantation in man. Transfer of responses to priming Ag has not been successful, although this would broaden the range of organisms to which recipients could be protected. To investigate the importance of T cells and Ag in such transfer we primed marrow donors with keyhole limpet hemocyanin (KLH) 1 or 3 wk before marrow harvesting. B cells secreting IgM and IgG anti-KLH antibody were present in donor marrow at both 1 and 3 wk after immunization. After T cell depletion, donor marrow was infused into chemo-irradiated recipients, half of whom were immunized pretransplant with KLH. We found no evidence for the transfer of the IgM component of the response. Clonal expansion of the transferred IgG antibody-secreting cells with a corresponding rise in recipient serum IgG antibody levels was seen only when donors were primed 3 wk before marrow harvest and when the recipients were also immunized. IEF and immunoblotting demonstrated that successful transfer coincided with maturation of the IgG primary response from a polyclonal to an oligoclonal pattern and confirmed that donor oligoclonal bands appeared in the recipient serum. We conclude that the immunization protocols required for the transfer of antibody responses to priming Ag reflect the initial dependence of unprimed B cells on T cell help and on prolonged Ag stimulation. Ag-stimulated primary B cells in T cell-depleted marrow respond only to the noncognate growth and differentiation signals available in the chemo-irradiated recipient after an initial period of clonal selection and expansion in the donor which is both T cell and Ag dependent. Even after this initial selection, continued expansion of antibody-secreting clones in recipients retains an absolute dependence on Ag stimulation. Immunization techniques to protect transplant recipients against organisms such as Pseudomonas and CMV may need to be modified accordingly.
Wimperis
J Z
JZ
Department of Haematology, Royal Free Hospital, Hampstead, London.
Gottlieb
D
D
Duncombe
A S
AS
Heslop
H E
HE
Prentice
H G
HG
Brenner
M K
MK
D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D008211:Lymphocyte Cooperation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D006433:Hemocyanins