On the molecular basis of T-helper-cell function. IV. B-lymphocyte-promotor factors: on their mode of action, biochemical nature and possible relationship to molecules involved in specific T-helper-cell activity.
Some further aspects of B-lymphocyte-promotor factor (B-LPF) activity have been studied. This activity was present in the supernatants of certain helper-T-cell lines, and it induced polyclonal activation of Ig+ B cells into Ig-secreting cells. It was found that B-LPF induced polyclonal, terminal B-cell differentiation (1) in T-cell- and macrophage-depleted spleen cell populations, (2) in both Lyb-5- and Lyb-5+ cells as well as in small and blast-like splenic B cells, and (3) in normal rather than memory B cells. B-LPF function was neither restricted to major histocompatibility complex gene products nor to immunoglobulin allotypes. B-LPF-like activity was also produced by some B-cell lymphomas/hybrids and by the P388-D1 macrophage line. B-LPF activity was found in three MW fractions: (I) greater than 180,000 (pI greater than 7.0 and 4.5-5.5); (II) 50,000-70,000 (pI greater than 7.0; 6.0-6.5, and 4.5-5.5); and (III) 10,000-15,000 (pI greater than 7.0). All three MW forms of B-LPF activity carried antiserum 6036-defined and AB-1.9.3 monoclonal antibody-defined determinants, and they reacted with chicken gammaglobulin (CGG)-Sepharose but not with human serum albumin-Sepharose. These data indicate that the three MW forms of B-LPF activity are associated/dissociated forms of a 10,000-15,000 MW form (subunit) rather than three different molecular species with B-LPF activity. A comparative study between antigen-specific helper factors and B-LPF was hampered by the finding that the helper-T-cell hybridomas used (e.g., T85-109-45/1) only produced B-LPF in our hands. Previously, it has been described that these helper-T-cell hybrids produced CGG-specific, I-Ak-restricted helper factors. However, one surprising observation was that B-LPF produced by both T85 hybrid cells and L12 T lymphoma cells was absorbed and could be eluted from CGG-Sepharose columns. The relationship of B-LPF to other nonspecific and apparently specific T-helper-cell products is discussed in particular in the light of the observations that many immunologically active molecules are built up from 10,000-12,000 molecular weight domain-like polypeptide structures.
Reininger
L
L
Fueri
J
J
Boned
A
A
Prat
M
M
Landolfo
S
S
Rubin
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D000939:Epitopes; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D006462:Hemolytic Plaque Technique; D006825:Hybridomas / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D008223:Lymphoma / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008970:Molecular Weight; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000939:Epitopes; D006133:Growth Substances; D007136:Immunoglobulins; D007376:Interleukin-2; D008222:Lymphokines; D015847:Interleukin-4