Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec 1;187(11):5712-9.
doi: 10.4049/jimmunol.1102416. Epub 2011 Oct 26.

Formation of B-1 B cells from neonatal B-1 transitional cells exhibits NF-κB redundancy

Encarnacion Montecino-Rodriguez  1 , Kenneth Dorshkind
Affiliations

Formation of B-1 B cells from neonatal B-1 transitional cells exhibits NF-κB redundancy

Encarnacion Montecino-Rodriguez et al. J Immunol. .

Abstract

The stages of development leading up to the formation of mature B-1 cells have not been identified. As a result, there is no basis for understanding why various genetic defects, and those in the classical or alternative NF-κB pathways in particular, differentially affect the B-1 and B-2 B cell lineages. In this article, we demonstrate that B-1 B cells are generated from transitional cell intermediates that emerge in a distinct neonatal wave of development that is sustained for ~2 wk after birth and then declines as B-2 transitional cells predominate. We further show that, in contrast to the dependence of B-2 transitional cells on the alternative pathway, the survival of neonatal B-1 transitional cells and their maturation into B-1 B cells occurs as long as either alternative or classical NF-κB signaling is intact. On the basis of these results, we have generated a model of B-1 development that allows the defects in B-1 and B-2 cell production observed in various NF-κB-deficient strains of mice to be placed into a coherent cellular context.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Most sIgM+ B cells in neonatal SPL are immature transitional cells. A, Representative FACS analyses showing T1 and T2/T3 transitional, follicular (FO), marginal zone (MZ), and B-1 cells in the spleen (SPL) of 6 week and 5 day old SW mice. B, Age related changes in the relative frequency of B cell populations within sIgM+ cells in SPL. T1 and FO cells were defined according to their levels of sIgM and CD21 expression as illustrated in Supplementary Fig. 1 (on line). C, Representative FACS analyses of B-2, B-1a and B-1b cells in the peritoneal cavity (PerC) of 6 week and 5 day old SW mice. D, Age related changes in the relative frequency of B cell populations within sIgM+ cells in the PerC. n indicates the number of animals processed at the indicated time points. Average frequency and s.d. values for older animals are provided in Supplementary Table I (on line).
FIGURE 2
FIGURE 2
Neonatal T1 and T2/T3 cells preferentially mature into B-1 cells. A, Immunoglobulin Variable Heavy chain 11 (VH11) usage in T1, T2/T3 and FO cells isolated from 5 day and 8 week old SW mice. Representative FACS analyses of PerC cells from SCID mice transplanted with T1 and T2/T3 SPL cells isolated from 4 day (B) and 8 week old (C) donors. Plots show populations gated on donor sIgMa+ sIgDa+ cells.
FIGURE 3
FIGURE 3
Age related changes in the B-1 potential of T1 and T2/T3 neonatal SPL cells. A, Relative frequency of B-1 and B-2 cells within donor sIgMa+ cells in the PerC of SCID mice transplanted with T1 and T2/T3 transitional cells isolated from the SPL of 5 and 12 days and 6 week old SW mice. B, Relative frequencies of B-1a and B-1b cells within the donor B-1 cells shown in panel (A). Note that neonatal transitional cells generate B-1a cells more efficiently than adult transitional cells. Differences in reconstitution between adult and neonatal populations were tested by two-tailed unpaired Student's t test (a=0.05), P values are indicated in parentheses. n indicates the number of animal tested at each time point. n indicates the number of recipients processed in each group.
FIGURE 4
FIGURE 4
Distribution of B-1a, B-1b and B-2 cells in the PerC of adult BAFF-R–/–, XID and NF-κB1–/–Mice. Representative FACS analyses and relative frequency of B-1a, B-1b and B-2 cells in the PerC of BAFF-R—/— (A), XID (B) and NF-κB1—/— (C) mice are shown. n indicates the number of animals processed in each group.
FIGURE 5
FIGURE 5
Neonatal B-1 Transitional Cells Emerge in BAFF-R—/—, XID and NF-kB1—/— Mice. Age related changes in the relative frequency of B cell populations within sIgM+ cells in the SPL of adult (A) and neonatal (B) BAFF-R—/— mice, adult (C) and neonatal (D) XID mice and adult (E) and neonatal (F) NF-kkB1—/—mice. n indicates the number of animals processed in each group. Average frequency and s.d. values for older animals are provided in Supplementary Table II (on line).
FIGURE 6
FIGURE 6
B-1 Transitional Cells From BAFF-R—/— and NF-κB1—/— Mice Mature into B-1 cells. A, Representative FACS analyses of the PerC cells from RAG-2/SJL mice transplanted with T1 and T2/T3 SPL cells from 5 day and 8 week old BAFF-R—/— donors. B, Relative frequency of B-1 and B-2 cells within donor CD45.2+ sIgM+ cells in the PerC of recipients of BAFF-R–/– transitional cells from 5 day (Neonates) and 8 week (Adults) old donors. C, Representative FACS analyses of the PerC cells from RAG-2/SJL mice transplanted with T1 and T2/T3 SPL cells from 7 day old NF-κB1—/— donors. D, B-1 and B-2 potential of 7 day old NF-kB1—/— T1 and T2/T3 SPL cells. The upper panel shows the frequency of B-1 and B-2 cells reconstituted and the lower panel shows the frequency of B-1a and B-1b cells within the B-1 populations in the upper panels. The data in all panels represent relative frequencies within donor CD45.2+ sIgM+ cells. n indicates the number of recipients processed in each group.
FIGURE 7
FIGURE 7
Model of layered B-1 and B-2 development. In a first neonatal wave, B-1 CLPs generate B-1 progenitors that in turn differentiate into immature B-1 cells. The latter cells then migrate to the SPL where they mature into B-1a and B-1b cells through B-1 transitional cell intermediates. In a second wave, B-2 CLPs generate immature B-2 cells that mature into B-2 transitional cells in the SPL. This B-2 transitional cell wave becomes predominant in the adult. Emergence of B-1 and B-2 transitional cells is blocked when both the classical and alternative NF-κB pathways are inactivated (Step 1). However, selective defects in one or the other pathway have differential effects on the formation of mature B-1 and B-2 cells. While the survival and maturation of B-2 transitional cells is dependent on alternative NF-κB signaling (step 2), B-1 transitional cells emerge and mature in the absence of these signals. The number of mature B-1 cells is reduced in mice with defects in classical NF-κB signaling. However, this does not compromise the emergence or maturation of B-1 transitional cells into B-1a or B-1b cells. Instead, classical signaling is required for maintenance of the mature B-1 pool, and for B-1a cells in particular, following their formation (step 3).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Allman D, Pillai S. Peripheral B Cell Subsets. Curr Opin Immunol. 2008;20:149–157. - PMC - PubMed
    1. Chung J, Sillverman M, Monroe J. Transitional B cells: step by step towards immune competence. Trends Immunol. 2003;24:343–349. - PubMed
    1. Carsetti R, Rosado MM, Wardmann H. Peripheral development of B cells in mouse and man. Immunol. Rev. 2004;197:179–191. - PubMed
    1. Thomas M, Srivastava B, Allman D. Regulation of peripheral B cell maturation. Cell Immunol. 2006;239:92–102. - PubMed
    1. Martin F, Kearney JF. Marginal-zone B cells. Nat. Rev. Immunol. 2002;2:323–335. - PubMed

Publication types