Synergy of helper factors in the differentiation of in vivo-preactivated antigen-specific human B cells.
After in vivo immunization with antigen, B cells appear in the peripheral blood which can be induced in vitro by nonspecific factors found in mixed lymphocyte culture supernatants (MLC-SN) to differentiate and secrete antibody specific for the immunizing antigen. In order to further delineate the nature of the factors involved in the differentiation of these in vivo-activated B cells, various helper factors, including interleukin 1 and interleukin 2 (IL-1 and IL-2), B-cell growth factor (BCGF), and B-cell differentiation factor (BCDF) were added separately and in combination to cultures of these preactivated B cells. T-cell-depleted fractions of peripheral blood mononuclear cells were obtained from normal individuals immunized in vivo with keyhole limpet hemocyanin. MLC-SN alone, without the addition of antigen, selectively triggered an antibody response specific for the antigen used to immunize in vivo in the absence of a polyclonal B-cell response. In order to obtain responses equal to those seen with MLC-SN, a combination of BCGF, IL-2, and BCDF was required, although any two factors partially reconstituted the response. Exogenous IL-1 had the least effect but was suppressive in the presence of optimal concentrations of monocytes. Thus, for maximal in vitro differentiation of in vivo-preactivated B cells, a combination of at least three helper factors is required and acts in a synergistic manner to induce antigen-specific antibody responses.
Peters
M
M
Butler
J L
JL
Margolick
J B
JB
Gerrard
T L
TL
Dinarello
C A
CA
Fauci
A S
AS
D001402:B-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000502:physiology; D002452:Cell Count; D002454:Cell Differentiation; D002469:Cell Separation; D000939:Epitopes; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000502:physiology*; D013997:Time Factors
D000939:Epitopes; D006133:Growth Substances; D007375:Interleukin-1; D007376:Interleukin-2; D008222:Lymphokines; D015847:Interleukin-4