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Critical Reviews™ in Immunology

Impact factor: 3.698

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v14.i3-4.20
pages 221-238

B-Cell Activation by Helper T-Cell Membranes

Marilyn R. Kehry
Department of Inflammatory Diseases, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877
Philip D. Hodgkin
The John Curtin School of Medical Research, Australian National University, Canberra, A.C.T. Australia 2601

ABSTRACT

Resting B cells can be stimulated to proliferate and differentiate to antibody-producing cells by the combination of cell contact and soluble signals provided by activated primed helper T (Th) cells. The ability of purified plasma membranes from activated Th cell clones and recombinant lymphokines to reconstitute B cell proliferation and differentiation has allowed an increased understanding of B cell activation and characterization of the molecules involved. B cell-Th cell contact appears sufficient for delivering the proliferative signal to B cells in the absence of lymphokines. A receptor ligand pair that plays a critical role in delivery of the contact signal is CD40 on the B cell surface and the ligand for CD40 on activated Th cells. Lymphokines alone do not drive resting B cell differentiation; however, when these soluble signals are delivered during the time of B cell DNA replication, they effect B cell differentiation and isotype switching. Delivery of the CD40-dependent contact signal to resting B cells appears to require a high degree of CD40 crosslinking on the B cell surface. Providing contact signals to naive B cells with recombinant molecules in membrane fractions may allow the generation of methodology to support the production of novel antibodies in vitro.