CD27 expression in the human splenic marginal zone: the infant marginal zone is populated by naive B cells

Abstract

The splenic marginal zone of adult humans contains B cells, of which most express CD27, an antigen only recently identified as a marker for somatically mutated memory B cells. We investigated whether and to which extent the developing marginal zone in infants and children is populated by either memory (CD27+) or naive (CD27-) B cells. Frozen sections of 32 spleens of infants and children ranging in age from 6 days to 15 years and 6 adult spleens were investigated. The expression of CD27 in combination with monoclonal antibodies against CD3, CD21, IgM, IgD and ASM-1 was analyzed by immunohistochemistry. The marginal zone was already present at 4 months after birth but CD21 expression was observed first after 2 years. CD27-positive marginal zone B cells were observed firstly 2 years after birth and increased in number to adult levels at the age of 5 years. We demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years. Before the age of 2 years, although present, memory B cells appear to be unable to colonize the marginal zone. Because of the absence of memory B cells in the marginal zone, the immune system of a child is not capable to initiate a rapid secondary humoral immune response comparable to the adult immune response.

Human IgM+CD27+ B Cells: Memory B Cells or “Memory” B Cells?

“…This led to the conclusion that CD27 expression identifies all human memory B cells. Consistent with earlier studies (15,16) (13,37), consistent with previous findings that: 1) human B cells in the splenic MZ expressed somatically mutated IgV region genes while those in the follicle were unmutated (38) (Fig. 1a); and 2) TD Ag-specific memory B cells in rats localize to the splenic MZ (39).…”

Evidence for preferential Ig gene usage and differential TdT and exonuclease activities in human naïve and memory B cells

“…Studies from several groups have suggested unique biological functions and possibly a unique developmental pathway of this group of cells Di Sabatino et al, 2004;Kruetzmann et al, 2003;Ma et al, 2006;Weller et al, 2004;Xiao et al, 2004;Zandvoort et al, 2001). Our data demonstrated that V H , D and J H gene segment usage in this type of memory B cells are broad and very similar to those of both naïve B cells and IgD − CD27 + memory B cells.…”

Human innate B cells: a link between host defense and autoimmunity?

“…Anatomically, however, a welldefined MZ compartment can be observed in infant spleens by 2 years of age. Interestingly, while in adults the vast majority of MZ B cells express the memory cell marker CD27 and express at least some level of somatic hypermutation, the infant MZ appears to be devoid of CD27 + B cells [22]. These observations need to be reconciled with the presence in the peripheral blood of children under 2 years of age of somatically mutated B cells with an IgM/ IgD MZ phenotype [23].…”