Direct interaction between an antigen-specific B cell clone and an MHC class II-reactive helper T cell clone.
TP67.14 established by somatic hybridization is a 2,4,6-trinitrobenzenesulfonic acid (trinitrophenyl, TNP)-specific B cell clone with a receptor molecule for TNP on the cell membrane, and MS202 is an interleukin-2 (IL-2)-dependent T helper (Th) cell clone reactive to auto-MHC class II antigens (IAk and IEk) as previously reported. In the present study it was shown that MS202 considerably induced the maturation of TP67.14 into anti-TNP plaque-forming cells (PFCs), and this response was markedly augmented by the addition of TNP-keyhole limpet hemocyanin (KLH). Recombinant cytokines and the culture supernatant of MS202 with TP67.14 did not affect the generation of anti-TNP antibodies by TP67.14. Also, neither anti-IL-4 nor anti-IL-5 monoclonal antibody (mAb) inhibited the maturation of TP67.14 mediated by MS202. The differentiative effect of MS202 on TP67.14 was completely lost when each cell was separately cultured using a semipermeable membrane. Monoclonal antibodies against LFA-1 beta molecules significantly blocked the development of anti-TNP PFCs induced by MS202, as well as anti-IAk and anti-IEk mAbs. Interestingly, the plasma membrane-enriched fraction (PM) derived from MS202 exhibited much more differentiative effects on TP67.14 treated with TNP-KLH than PM from other T cell lines and concanavalin A-induced T lymphoblasts. In addition, TNP-conjugated PM from MS202 by itself induced a great number of anti-TNP PFCs. The present findings indicate that MS202 is capable of inducing the maturation of TP67.14, which is considered to represent a population of B cells with antigen specificity in a late lineage of B cell maturation, through direct cell contact but not soluble factors. This suggests that B cells with antigen specificity, in the presence of antigen, can be induced to mature into antibody-secreting cells through direct contact with Th cells; in this process surface major histocompatibility complex class II and lymphocyte function-associated antigen 1 (LFA-1) molecules are directly involved and the cell membrane derived from Th cells provides a transductional signal for maturation of B cells with antigen specificity in the presence of antigen.
Hamano
T
T
Second Department of Internal Medicine, Hyogo College of Medicine, Japan.
Asano
Y
Y
Iwasaki
T
T
Yamasaki
T
T
Hase
K
K
Kakishita
E
E
D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000502:physiology; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
D000954:Antigens, Surface; D016207:Cytokines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D014301:Trinitrobenzenes