Journal
INTERNATIONAL IMMUNOLOGY
Volume 13, Issue 12, Pages 1583-1593Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/13.12.1583
Keywords
antigen presentation; B cell-deficient mice; clonal expansion; T-B cell collaboration; T cell activation
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Funding
- NCI NIH HHS [R01-CA50777] Funding Source: Medline
- NIAID NIH HHS [2 T32 AI 07403-07] Funding Source: Medline
- NIGMS NIH HHS [GM19331] Funding Source: Medline
- NINDS NIH HHS [5 R01 NS38272] Funding Source: Medline
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Studies in B cell-deficient mice generated by continuous injection of anti-mu antibodies (mu SM) 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 (mu MT). In this study we show that in the absence of B cells, T cell responses are greatly reduced in all the available mu MT mouse strains although responses in mu MT of the C57BL/6 background (which were used for most studies with mu MT) were much more variable and could reach up to 42% of control. In contrast, T cell responses in mu MT --> F-1 bone marrow chimeras which have the same phenotype as mu MT were totally impaired, suggesting a principle difference between mice developing without B cells (mu MT mice) and mu SM which are made B cell deficient only after birth. Normal T cell priming was completely restored by reconstitution of mu MT and mu MT --> 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.
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