Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations

Int Immunol. 2001 Dec;13(12):1583-93. doi: 10.1093/intimm/13.12.1583.

Abstract

Studies in B cell-deficient mice generated by continuous injection of anti-mu antibodies (muSM) showed that T cell priming in lymph nodes was dependent on antigen presentation by B cells. This concept has recently become controversial since a wide range, from complete deficiency to near normal T cell responses, was reported in studies carried out with B cell-deficient mice generated by gene disruption (muMT). In this study we show that in the absence of B cells, T cell responses are greatly reduced in all the available muMT mouse strains although responses in muMT of the C57BL/6 background (which were used for most studies with muMT) were much more variable and could reach up to 42% of control. In contrast, T cell responses in muMT --> F(1) bone marrow chimeras which have the same phenotype as muMT were totally impaired, suggesting a principle difference between mice developing without B cells (muMT mice) and muSM which are made B cell deficient only after birth. Normal T cell priming was completely restored by reconstitution of muMT and muMT --> F(1) mice with syngeneic B cells. Interestingly, only B cell populations containing antigen-specific B cells were capable of reconstituting T cell responses. Monoclonal B cells taken from Ig transgenic mice could not reconstitute responses to an irrelevant antigen. We also found that B cells were also required for systemic T cell priming when antigen concentrations were limiting but were not required for priming (for T cell help) when mice were immunized with a high antigen dose.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism*
  • Antigen-Presenting Cells / transplantation
  • Antigens / administration & dosage*
  • Antigens / immunology
  • Antigens / metabolism
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / transplantation
  • Bone Marrow / immunology
  • Cell Differentiation / immunology
  • Crosses, Genetic
  • Dose-Response Relationship, Immunologic
  • Epitopes, B-Lymphocyte / immunology*
  • Female
  • Hemocyanins / immunology
  • Hypersensitivity, Delayed / immunology
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muramidase / immunology
  • Radiation Chimera / immunology
  • Receptors, Antigen, B-Cell / immunology
  • Species Specificity
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology

Substances

  • Antigens
  • Epitopes, B-Lymphocyte
  • Receptors, Antigen, B-Cell
  • Hemocyanins
  • hen egg lysozyme
  • Muramidase
  • keyhole-limpet hemocyanin