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B-cell activity in children with malaria
Jackson C Korir1, Japhet K Magambo, Joseph K Mwatha
1Walter Reed Project/Kenya Medical Research Institute, Kisumu, Kenya.
Insights
Severe malaria anaemia involves increased B-cell proliferation and complement deposition, leading to the loss of B-cell CD21. This membrane-bound CD21 loss, crucial in malaria pathophysiology, is not due to classical enzymatic cleavage.
Area of Science:
- Immunology
- Hematology
- Infectious Diseases
Background:
- Red blood cell (RBC) complement regulatory proteins (CR1 and CD55) deficiency is linked to malarial anemia.
- This study investigates the role of B cell CD21, which shares functional similarities with RBC CR1, in malaria.
Purpose of the Study:
- To explore the involvement of B cell CD21 in the pathophysiology of severe malaria anemia (SMA).
- To compare B cell characteristics, including CD21 expression and complement deposition, between children with SMA and uncomplicated malaria (UM).
Main Methods:
- Case-control study in Kenya involving children with SMA and UM.
- Flow cytometry assessed B cell numbers (CD20+), CD21 expression, and C3dg deposition.
- ELISA measured soluble CD21 (sCD21) levels.
- Paired t tests were used for statistical analysis.
Main Results:
- Children with SMA exhibited higher lymphocyte counts and a greater number/percentage of activated B cells (CD20+).
- SMA patients showed significantly lower median fluorescence intensity of membrane-bound CD21 and increased C3dg deposition on B cells.
- Soluble CD21 levels were unexpectedly lower in SMA patients, suggesting CD21 shedding without release into circulation.
Conclusions:
- B cell involvement, characterized by increased proliferation, complement deposition, and loss of membrane-bound CD21, is implicated in severe malaria pathophysiology.
- The observed loss of CD21 on B cells in SMA is likely mediated by complement and does not follow classical enzymatic cleavage pathways.
Background:
Recent studies implicate deficiency of red blood cell (RBC) complement regulatory proteins (CR1 and CD55) in the pathogenesis of malarial anaemia. This study explored the involvement of B cell CD21, which has an analogous role to RBC CR1.
Methods:
In a case control study conducted in Kisumu District hospital, western Kenya, children with severe malaria anaemia (SMA) and those with uncomplicated malaria (UM) were assessed by flow cytometry for B cells (CD20+) numbers, expression levels of CD21 and deposition of C3dg and by ELISA for soluble CD21 (sCD21). Paired t tests were used to determine statistical significance at a = 0.05.
Results:
Children with SMA had significantly higher lymphocyte count (9,627.7 ± 8786.1 SD vs. 5,507 ± 2436 SD, P = 0.04 in the UM group) and the computed geometric mean of mature B-cell numbers based on the absolute lymphocyte count was significantly higher for SMA group: 1,823 (1,126 to 2,982, 95% CI) and 826.6 (564 to 1,220, 95% CI)] for UM group (P = 0.003). SMA group also had a higher percentage of CD20+ B cells (26.8 ± 9.7SD vs 20.9 ± 9.01 SD in the UM) (P = 0.03), indicating considerable polyclonal B-cell activation. The CD21 median flourescence intensity was lower in the SMA (246.4 ± 87.4 SD vs 369 ± 137.7 SD) (P <0.0001), probably due to complement mediated shaving of CD21 by fixed tissue macrophages. The CD20+ B cells of SMAs had higher levels of the complement split product C3dg (18.35 ± 10 SD vs 11.5 ± 6.8 S.D), (P = 0.0002), confirming possible role of complement in CD21 removal. Unexpectedly, the SMAs had lower levels of sCD21 (226.5 ± 131.5 SD vs 341.4 ± 137.3 SD in the UM) (P < 0.0001), indicating that the shaved CD21 is not released to peripheral circulation.
Conclusions:
These results implicate B-cell in pathophysiology of severe malaria that involves increased B-cell proliferation, increased complement deposition and subsequent loss of membrane-bound CD21. The loss of CD21 is not by the classical enzmatic cleavage.
