Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria

Abstract

In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weight ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection, in parallel to the parasitaemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced) stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced) triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that the polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.

Splenic architecture disruption and parasite-induced splenocyte activation and anergy in Plasmodium falciparum-infected Saimiri sciureus monkeys

“…Follicle disarray with disturbance of germinal centre architecture responses in Saimiri was similar to the findings reported in human [ 34 ] and murine ( Plasmodium berghei , Plasmodium chabaudi ) malarias [ 19 , 51 ] and therefore it appears to be an universal feature of malaria infections. Follicles remained enlarged and composed mainly by activated B cells 15 days after the start of chloroquine treatment, which is consistent with a status of spontaneous polyclonal B cell activation previously demonstrated both in rodent and human malaria [ 52 - 54 ].…”

The prevalence of autoantibodies in an elderly sub-Saharan African population

“…It is also well known that chronic exposure to malarial parasites can lead to polyclonal stimulation of immunoglobulin cells and thus to an increased frequency of AAb [50]. The polyclonal B‐cell activation that takes place during the course of infection may appear as a result of successive waves of antigen‐specific B‐cell activation [51]. All participants had high levels of antimalarial antibodies.…”

Malaria, a difficult diagnosis in a febrile patient with sub-microscopic parasitaemia and polyclonal lymphocyte activation outside the endemic region, in Brazil

“…Acute and chronic malaria, in both rodent experimental models [ 22 , 23 ] and natural human disease [ 24 ], are, indeed, usually accompanied by a nonspecific PBA that is reflected by a marked increase in the concentration of immunoglobulins (IgM and IgG) and the presence of antibodies against antigens not related to the parasite, including auto-antigens, in the patient’s serum [ 25 ]. PBA most likely results from a generalised stimulation of T- and B-lymphocytes by plasmodial antigens endowed with mitogenic properties [ 26 ], which are released during the course of infection.…”