Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

Abstract

CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG + B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27+ to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27-IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenzaspecific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27 -IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27- B cells.