- Paper Report
- Open Access
Organogenic role of B lymphocytes in mucosal immunity
- Thomas Dorner1
© Current Science Ltd 2000
- Published: 5 January 2000
- B cells
- Peyer's patches
Gut-associated lymphoid tissue (GALT) consists of highly organized Peyer's patches (PPs) in the small intestine and intra-epithelial lymphocytes. The intestinal surface of PPs is characterized by the presence of follicle-associated epithelium (FAE)-covering "domes", regions lacking intestinal villi. M cells are found in these domes lacking microvilli on their apical surface. Therefore, the term M denotes microfold or membranous cells that are able to tunnel pathogens through the cytoplasm to the basal surface, allowing close contact with lymphocytes and macrophages. It has been shown that M cells of the respiratory epithelium can serve as the entrance gates for pathogens, such as mycobacteria (Teitelbaum et al, Immunity 1999, 10:641-50 [Abstract]). Previous in vitro studies showed that a B-cell lymphoma could effectively convert epithelial cells into M cells. This study analyzed whether B cells are responsible for the generation of FAE and M cells in vivoand whether B cell deficiency could affect transepithelial transport of an enterally-transmitted retrovirus.
Lack of B cells, due to knockout of either the ? membrane segment (Igh-6) or JH segments of Ig genes (JHD), caused a diminution of detectable PPs, whereas TCR-deficient mice, independently of the TCR subtype, had normal numbers of PPs. The strongest PP deficiency was observed in mice lacking both B and T cells (RAG1 KO mice). In B-cell-negative mice, the size of PPs was much smaller and FAE was abnormal. Transgenic expression of a membrane-bound IgM (mIgM) on the JHD background, allowing generation of B cells with surface but not secreted IgM, could be shown to completely restore the development of PPs and FAE.
Whereas M cells could be found in abundance in the large domes in the PPs of normal mice, only a few cells with a characteristic microfold surface could be detected in the smaller domes of B-cell-deficient animals. In addition, cells with an unusual brush border, most likely M cell maturation intermediates, were identified in mice without B cells. Reconstitution of B cells by mIgM transgene expression resulted in the complete development of both FAE and M cells. Absence of sufficient T cells did not have any significant influence on FAE and M cell development. Finally, RAG1 KO mice did not develop proper domes and lacked M cells.
Elimination of either T cells, with appropriate V chains, or B cells abrogated MMTV infection. Thus, B cells may be needed both for T cell activation and for M-cell-dependent translocation of MMTV. Chimeras with a reconstituted immune system but with underdeveloped FAE were shown to be significantly resistant to MMTV infection. In all TCR KO (having intact B and M cells) recipients of B6 bone marrow, MMTV infection was readily detectable.
The authors examined knockout (KO) mice with targeted mutations that lack the following specific lymphocyte subsets: 1, the absence of B cells, due to KO of either the ? membrane segment (Igh-6) or JH segments of immunoglobulin genes (Ig)(JHD); 2, mice deficient in either a?T cells or d?T cells; and 3, mice deficient in both a? and d?T cells. In addition, mice lacking both B and T cells as a result of the absence of RAG1 recombinase (RAG1 KO) were analyzed for the development of PPs by light and laser scanning microscopy and the numbers of M cells were also analyzed by scanning microscopy. Since substantial diminution of M cell numbers should lead to a strong functional impairment, mouse mammary tumor virus (MMTV), a classic retrovirus using M cells to enter GALT, was applied to analyze the involvement of M cells in retroviral transport from the intestinal lumen. To unmask the possible role of M cells in channeling MMTV through the intestinal wall, a bone marrow chimera approach was used (newborn Igh-6 or T cell receptor (TCR) KO mice as recipients of normal adult B6).