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Selective impairment of B cell function by Neisseria meningitidis
Abstract:
Spleen cells from CBA/J mice infected with Neisseria meningitidis displayed depressed in vitro plaque-forming cell (PFC) responses to T-dependent (sheep red blood cell; SRBC) and T-independent (TNP-LPS, TNP-Ficoll) antigens. The inhibition was observed over a wide range of antigen concentrations. The decreased responsiveness of splenocytes from infected mice was due to a selective impairment of B-cell function since helper-T-cell activity was intact in infected mice as shown by the ability of T-enriched lymphocytes to cooperate with normal B-enriched lymphocytes in the generation of an anti-SRBC response, accessory macrophage function was preserved since adherent spleen cells from bacteria-injected mice were shown to produce normal or increased levels of IL-1 and were able to cooperate with normal non-adherent spleen cells in the generation of PFC against SRBC. Addition of peritoneal cells from normal animals or extraneous IL-1 both failed to restore normal PFC responses in cultures of splenocytes from infected mice. Finally, B-enriched lymphocytes from infected mice produced poor anti-SRBC responses when cultured with either Con A supernatant or T-enriched lymphocytes from normal or infected mice. Cell-mixing experiments failed to detect the presence of suppressor cells in cultures of unfractionated spleen cells or B-enriched lymphocytes from infected mice. Therefore, the immunological unresponsiveness associated with a Neisseria meningitidis infection was attributed to a meningococcus-induced defect(s) in B-cell function. In vivo polyclonal B-cell activation leading to clonal exhaustion did not play a major role in the depression of humoral responses since meningococcal infection induced little or no polyclonal Ig secretion.
Insights
Neisseria meningitidis infection impairs B-cell function, leading to reduced immune responses. This study found no evidence of suppressor cells or clonal exhaustion, attributing unresponsiveness to a direct defect in B-cells.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Neisseria meningitidis is a significant human pathogen.
- Bacterial infections can modulate host immune responses.
- Understanding immune defects is crucial for managing infectious diseases.
Purpose of the Study:
- To investigate the immunological unresponsiveness in mice infected with Neisseria meningitidis.
- To determine the specific immune cell type responsible for the depressed responses.
- To elucidate the mechanism behind the impaired humoral immunity.
Main Methods:
- Infection of CBA/J mice with Neisseria meningitidis.
- In vitro assessment of plaque-forming cell (PFC) responses to T-dependent and T-independent antigens.
- Cell fractionation to isolate B-cells, T-cells, and macrophages.
- Co-culture experiments to assess cell cooperation and function.
- Analysis of Interleukin-1 (IL-1) production.
Main Results:
- Splenocytes from infected mice showed significantly reduced PFC responses to both T-dependent (sheep red blood cell; SRBC) and T-independent (TNP-LPS, TNP-Ficoll) antigens.
- Helper T-cell activity and accessory macrophage function (including IL-1 production) remained intact in infected mice.
- B-enriched lymphocytes from infected mice exhibited poor responses when cultured with normal T-cells or T-cell supernatants.
- Cell-mixing experiments did not reveal the presence of suppressor cells.
Conclusions:
- The immunological unresponsiveness observed during Neisseria meningitidis infection is primarily due to a defect in B-cell function.
- The impairment of B-cell function is directly induced by the meningococcus.
- Polyclonal B-cell activation and subsequent clonal exhaustion do not play a major role in the observed depression of humoral responses.